Sample records for regulates phototropic signal

  1. Phototropism: at the crossroads of light-signaling pathways.

    PubMed

    Goyal, Anupama; Szarzynska, Bogna; Fankhauser, Christian

    2013-07-01

    Phototropism enables plants to orient growth towards the direction of light and thereby maximizes photosynthesis in low-light environments. In angiosperms, blue-light photoreceptors called phototropins are primarily involved in sensing the direction of light. Phytochromes and cryptochromes (sensing red/far-red and blue light, respectively) also modulate asymmetric hypocotyl growth, leading to phototropism. Interactions between different light-signaling pathways regulating phototropism occur in cryptogams and angiosperms. In this review, we focus on the molecular mechanisms underlying the co-action between photosensory systems in the regulation of hypocotyl phototropism in Arabidopsis thaliana. Recent studies have shown that phytochromes and cryptochromes enhance phototropism by controlling the expression of important regulators of phototropin signaling. In addition, phytochromes may also regulate growth towards light via direct interaction with the phototropins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Role of the phytochrome and cryptochrome signaling pathways in hypocotyl phototropism.

    PubMed

    Tsuchida-Mayama, Tomoko; Sakai, Tatsuya; Hanada, Atsushi; Uehara, Yukiko; Asami, Tadao; Yamaguchi, Shinjiro

    2010-05-01

    Unilateral blue-light irradiation activates phototropin (phot) photoreceptors, resulting in asymmetric distribution of the phytohormone auxin and induction of a phototropic response in higher plants. Other photoreceptors, including phytochrome (phy) and cryptochrome (cry), have been proposed as modulators of phototropic responses. We show here that either phy or cry is required for hypocotyl phototropism in Arabidopsis thaliana under high fluence rates of blue light, and that constitutive expression of ROOT PHOTOTROPISM 2 (RPT2) and treatment with the phytohormone gibberellin (GA) biosynthesis inhibitor paclobutrazol partially and independently complement the non-phototropic hypocotyl phenotype of the phyA cry1 cry2 mutant under high fluence rates of blue light. Our results indicate that induction of RPT2 and reduction in the GA are crucial for hypocotyl phototropic regulation by phy and cry. We also show that GA suppresses hypocotyl bending via destabilization of DELLA transcriptional regulators under darkness, but does not suppress the phototropic response in the presence of either phyA or cryptochromes, suggesting that these photoreceptors control not only the GA content but also the GA sensing and/or signaling that affects hypocotyl phototropism. The metabolic and signaling regulation of not only auxin but also GA by photoreceptors therefore appears to determine the hypocotyl growth pattern, including phototropic and gravitropic responses and inhibition of hypocotyl elongation, for adaptation to various light environments.

  3. Nuclear phytochrome A signaling promotes phototropism in Arabidopsis.

    PubMed

    Kami, Chitose; Hersch, Micha; Trevisan, Martine; Genoud, Thierry; Hiltbrunner, Andreas; Bergmann, Sven; Fankhauser, Christian

    2012-02-01

    Phototropin photoreceptors (phot1 and phot2 in Arabidopsis thaliana) enable responses to directional light cues (e.g., positive phototropism in the hypocotyl). In Arabidopsis, phot1 is essential for phototropism in response to low light, a response that is also modulated by phytochrome A (phyA), representing a classical example of photoreceptor coaction. The molecular mechanisms underlying promotion of phototropism by phyA remain unclear. Most phyA responses require nuclear accumulation of the photoreceptor, but interestingly, it has been proposed that cytosolic phyA promotes phototropism. By comparing the kinetics of phototropism in seedlings with different subcellular localizations of phyA, we show that nuclear phyA accelerates the phototropic response, whereas in the fhy1 fhl mutant, in which phyA remains in the cytosol, phototropic bending is slower than in the wild type. Consistent with this data, we find that transcription factors needed for full phyA responses are needed for normal phototropism. Moreover, we show that phyA is the primary photoreceptor promoting the expression of phototropism regulators in low light (e.g., PHYTOCHROME KINASE SUBSTRATE1 [PKS1] and ROOT PHOTO TROPISM2 [RPT2]). Although phyA remains cytosolic in fhy1 fhl, induction of PKS1 and RPT2 expression still occurs in fhy1 fhl, indicating that a low level of nuclear phyA signaling is still present in fhy1 fhl.

  4. PINOID functions in root phototropism as a negative regulator

    PubMed Central

    Haga, Ken; Sakai, Tatsuya

    2015-01-01

    The PINOID (PID) family, which belongs to AGCVIII kinases, is known to be involved in the regulation of auxin efflux transporter PIN-FORMED (PIN) proteins through changes in the phosphorylation status. Recently, we demonstrated that the PID family is necessary for phytochrome-mediated phototropic enhancement in Arabidopsis hypocotyls and that the downregulation of PID expression by red-light pretreatment results in the promotion of the PIN-mediated auxin gradient during phototropic responses. However, whether PID participates in root phototropism in Arabidopsis seedlings has not been well studied. Here, we demonstrated that negative root phototropic responses are enhanced in the pid quadruple mutant and are severely impaired in transgenic plants expressing PID constitutively. The results indicate that the PID family functions in a negative root phototropism as a negative regulator. On the other hand, analysis with PID fused to a yellow fluorescent protein, VENUS, showed that unilateral blue-light irradiation causes a lower accumulation of PID proteins on the shaded side than on the irradiated side. This result suggests that the blue-light-mediated asymmetrical distribution of PID proteins may be one of the critical responses in phototropin-mediated signals during a negative root phototropism. Alternatively, such a transverse gradient of PID proteins may result from gravitropic stimulation produced by phototropic bending. PMID:26039488

  5. PINOID functions in root phototropism as a negative regulator.

    PubMed

    Haga, Ken; Sakai, Tatsuya

    2015-01-01

    The PINOID (PID) family, which belongs to AGCVIII kinases, is known to be involved in the regulation of auxin efflux transporter PIN-formed (PIN) proteins through changes in the phosphorylation status. Recently, we demonstrated that the PID family is necessary for phytochrome-mediated phototropic enhancement in Arabidopsis hypocotyls and that the downregulation of PID expression by red-light pretreatment results in the promotion of the PIN-mediated auxin gradient during phototropic responses. However, whether PID participates in root phototropism in Arabidopsis seedlings has not been well studied. Here, we demonstrated that negative root phototropic responses are enhanced in the pid quadruple mutant and are severely impaired in transgenic plants expressing PID constitutively. The results indicate that the PID family functions in a negative root phototropism as a negative regulator. On the other hand, analysis with PID fused to a yellow fluorescent protein, VENUS, showed that unilateral blue-light irradiation causes a lower accumulation of PID proteins on the shaded side than on the irradiated side. This result suggests that the blue-light-mediated asymmetrical distribution of PID proteins may be one of the critical responses in phototropin-mediated signals during a negative root phototropism. Alternatively, such a transverse gradient of PID proteins may result from gravitropic stimulation produced by phototropic bending.

  6. Nuclear Phytochrome A Signaling Promotes Phototropism in Arabidopsis[W][OA

    PubMed Central

    Kami, Chitose; Hersch, Micha; Trevisan, Martine; Genoud, Thierry; Hiltbrunner, Andreas; Bergmann, Sven; Fankhauser, Christian

    2012-01-01

    Phototropin photoreceptors (phot1 and phot2 in Arabidopsis thaliana) enable responses to directional light cues (e.g., positive phototropism in the hypocotyl). In Arabidopsis, phot1 is essential for phototropism in response to low light, a response that is also modulated by phytochrome A (phyA), representing a classical example of photoreceptor coaction. The molecular mechanisms underlying promotion of phototropism by phyA remain unclear. Most phyA responses require nuclear accumulation of the photoreceptor, but interestingly, it has been proposed that cytosolic phyA promotes phototropism. By comparing the kinetics of phototropism in seedlings with different subcellular localizations of phyA, we show that nuclear phyA accelerates the phototropic response, whereas in the fhy1 fhl mutant, in which phyA remains in the cytosol, phototropic bending is slower than in the wild type. Consistent with this data, we find that transcription factors needed for full phyA responses are needed for normal phototropism. Moreover, we show that phyA is the primary photoreceptor promoting the expression of phototropism regulators in low light (e.g., PHYTOCHROME KINASE SUBSTRATE1 [PKS1] and ROOT PHOTO TROPISM2 [RPT2]). Although phyA remains cytosolic in fhy1 fhl, induction of PKS1 and RPT2 expression still occurs in fhy1 fhl, indicating that a low level of nuclear phyA signaling is still present in fhy1 fhl. PMID:22374392

  7. PIF4 and PIF5 transcription factors link blue light and auxin to regulate the phototropic response in Arabidopsis.

    PubMed

    Sun, Jiaqiang; Qi, Linlin; Li, Yanan; Zhai, Qingzhe; Li, Chuanyou

    2013-06-01

    Both blue light (BL) and auxin are essential for phototropism in Arabidopsis thaliana. However, the mechanisms by which light is molecularly linked to auxin during phototropism remain elusive. Here, we report that phytochrome interacting factoR4 (PIF4) and PIF5 act downstream of the BL sensor phototropin1 (PHOT1) to negatively modulate phototropism in Arabidopsis. We also reveal that PIF4 and PIF5 negatively regulate auxin signaling. Furthermore, we demonstrate that PIF4 directly activates the expression of the auxin/indole-3-acetic acid (IAA) genes IAA19 and IAA29 by binding to the G-box (CACGTG) motifs in their promoters. Our genetic assays demonstrate that IAA19 and IAA29, which physically interact with auxin response factor7 (ARF7), are sufficient for PIF4 to negatively regulate auxin signaling and phototropism. This study identifies a key step of phototropic signaling in Arabidopsis by showing that PIF4 and PIF5 link light and auxin.

  8. Role of inositol 1,4,5-triphosphate signalling in gravitropic and phototropic gene expression.

    PubMed

    Salinas-Mondragon, Raul E; Kajla, Jyoti D; Perera, Imara Y; Brown, Christopher S; Sederoff, Heike Winter

    2010-12-01

    Plants sense light and gravity to orient their direction of growth. One common component in the early events of both phototropic and gravitropic signal transduction is activation of phospholipase C (PLC), which leads to an increase in inositol 1,4,5-triphosphate (InsP(3)) levels. The InsP(3) signal is terminated by hydrolysis of InsP(3) through inositolpolyphosphate-5-phosphatases (InsP 5-ptases). Arabidopsis plants expressing a heterologous InsP 5-ptase have low basal InsP(3) levels and exhibit reduced gravitropic and phototropic bending. Downstream effects of InsP(3)-mediated signalling are not understood. We used comparative transcript profiling to characterize gene expression changes in gravity- or light-stimulated Arabidopsis root apices that were manipulated in their InsP(3) metabolism either through inhibition of PLC activity or expression of InsP 5-ptase. We identified InsP(3)-dependent and InsP(3)-independent co-regulated gene sets in response to gravity or light stimulation. Inhibition of PLC activity in wild-type plants caused similar changes in transcript abundance in response to gravitropic and phototropic stimulation as in the transgenic lines. Therefore, we conclude that changes in gene expression in response to gravitropic and phototropic stimulation are mediated by two signal transduction pathways that vary in their dependence on changes in InsP(3). © 2010 Blackwell Publishing Ltd.

  9. PIF4 and PIF5 Transcription Factors Link Blue Light and Auxin to Regulate the Phototropic Response in Arabidopsis[C][W][OPEN

    PubMed Central

    Sun, Jiaqiang; Qi, Linlin; Li, Yanan; Zhai, Qingzhe; Li, Chuanyou

    2013-01-01

    Both blue light (BL) and auxin are essential for phototropism in Arabidopsis thaliana. However, the mechanisms by which light is molecularly linked to auxin during phototropism remain elusive. Here, we report that PHYTOCHROME INTERACTING FACTOR4 (PIF4) and PIF5 act downstream of the BL sensor PHOTOTROPIN1 (PHOT1) to negatively modulate phototropism in Arabidopsis. We also reveal that PIF4 and PIF5 negatively regulate auxin signaling. Furthermore, we demonstrate that PIF4 directly activates the expression of the AUXIN/INDOLE-3-ACETIC ACID (IAA) genes IAA19 and IAA29 by binding to the G-box (CACGTG) motifs in their promoters. Our genetic assays demonstrate that IAA19 and IAA29, which physically interact with AUXIN RESPONSE FACTOR7 (ARF7), are sufficient for PIF4 to negatively regulate auxin signaling and phototropism. This study identifies a key step of phototropic signaling in Arabidopsis by showing that PIF4 and PIF5 link light and auxin. PMID:23757399

  10. Phototropism: growing towards an understanding of plant movement.

    PubMed

    Liscum, Emmanuel; Askinosie, Scott K; Leuchtman, Daniel L; Morrow, Johanna; Willenburg, Kyle T; Coats, Diana Roberts

    2014-01-01

    Phototropism, or the differential cell elongation exhibited by a plant organ in response to directional blue light, provides the plant with a means to optimize photosynthetic light capture in the aerial portion and water and nutrient acquisition in the roots. Tremendous advances have been made in our understanding of the molecular, biochemical, and cellular bases of phototropism in recent years. Six photoreceptors and their associated signaling pathways have been linked to phototropic responses under various conditions. Primary detection of directional light occurs at the plasma membrane, whereas secondary modulatory photoreception occurs in the cytoplasm and nucleus. Intracellular responses to light cues are processed to regulate cell-to-cell movement of auxin to allow establishment of a trans-organ gradient of the hormone. Photosignaling also impinges on the transcriptional regulation response established as a result of changes in local auxin concentrations. Three additional phytohormone signaling pathways have also been shown to influence phototropic responsiveness, and these pathways are influenced by the photoreceptor signaling as well. Here, we will discuss this complex dance of intra- and intercellular responses that are regulated by these many systems to give rise to a rapid and robust adaptation response observed as organ bending.

  11. Phototropism: Growing towards an Understanding of Plant Movement[OPEN

    PubMed Central

    Liscum, Emmanuel; Askinosie, Scott K.; Leuchtman, Daniel L.; Morrow, Johanna; Willenburg, Kyle T.; Coats, Diana Roberts

    2014-01-01

    Phototropism, or the differential cell elongation exhibited by a plant organ in response to directional blue light, provides the plant with a means to optimize photosynthetic light capture in the aerial portion and water and nutrient acquisition in the roots. Tremendous advances have been made in our understanding of the molecular, biochemical, and cellular bases of phototropism in recent years. Six photoreceptors and their associated signaling pathways have been linked to phototropic responses under various conditions. Primary detection of directional light occurs at the plasma membrane, whereas secondary modulatory photoreception occurs in the cytoplasm and nucleus. Intracellular responses to light cues are processed to regulate cell-to-cell movement of auxin to allow establishment of a trans-organ gradient of the hormone. Photosignaling also impinges on the transcriptional regulation response established as a result of changes in local auxin concentrations. Three additional phytohormone signaling pathways have also been shown to influence phototropic responsiveness, and these pathways are influenced by the photoreceptor signaling as well. Here, we will discuss this complex dance of intra- and intercellular responses that are regulated by these many systems to give rise to a rapid and robust adaptation response observed as organ bending. PMID:24481074

  12. PHYTOCHROME KINASE SUBSTRATE1 regulates root phototropism and gravitropism.

    PubMed

    Boccalandro, Hernán E; De Simone, Silvia N; Bergmann-Honsberger, Ariane; Schepens, Isabelle; Fankhauser, Christian; Casal, Jorge J

    2008-01-01

    Light promotes the expression of PHYTOCHROME KINASE SUBSTRATE1 (PKS1) in the root of Arabidopsis thaliana, but the function of PKS1 in this organ is unknown. Unilateral blue light induced a negative root phototropic response mediated by phototropin 1 in wild-type seedlings. This response was absent in pks1 mutants. In the wild type, unilateral blue light enhanced PKS1 expression in the subapical region of the root several hours before bending was detectable. The negative phototropism and the enhanced PKS1 expression in response to blue light required phytochrome A (phyA). In addition, the pks1 mutation enhanced the root gravitropic response when vertically oriented seedlings were placed horizontally. The negative regulation of gravitropism by PKS1 occurred even in dark-grown seedlings and did not require phyA. Blue light also failed to induce negative phototropism in pks1 under reduced gravitational stimulation, indicating that the effect of pks1 on phototropism is not simply the consequence of the counteracting effect of enhanced gravitropism. We propose a model where the background level of PKS1 reduces gravitropism. After a phyA-dependent increase in its expression, PKS1 positively affects root phototropism and both effects contribute to negative curvature in response to unilateral blue light.

  13. Genetic separation of phototropism and blue light inhibition of stem elongation

    NASA Technical Reports Server (NTRS)

    Liscum, E.; Young, J. C.; Poff, K. L.; Hangarter, R. P.

    1992-01-01

    Blue light-induced regulation of cell elongation is a component of the signal response pathway for both phototropic curvature and inhibition of stem elongation in higher plants. To determine if blue light regulates cell elongation in these responses through shared or discrete pathways, phototropism and hypocotyl elongation were investigated in several blue light response mutants in Arabidopsis thaliana. Specifically, the blu mutants that lack blue light-dependent inhibition of hypocotyl elongation were found to exhibit a normal phototropic response. In contrast, a phototropic null mutant (JK218) and a mutant that has a 20- to 30-fold shift in the fluence dependence for first positive phototropism (JK224) showed normal inhibition of hypocotyl elongation in blue light. F1 progeny of crosses between the blu mutants and JK218 showed normal phototropism and inhibition of hypocotyl elongation, and approximately 1 in 16 F2 progeny were double mutants lacking both responses. Thus, blue light-dependent inhibition of hypocotyl elongation and phototropism operate through at least some genetically distinct components.

  14. A brassinosteroid-hypersensitive mutant of BAK1 indicates that a convergence of photomorphogenic and hormonal signaling modulates phototropism.

    PubMed

    Whippo, Craig W; Hangarter, Roger P

    2005-09-01

    The phototropic response of Arabidopsis (Arabidopsis thaliana) is induced by the phototropin photoreceptors and modulated by the cryptochrome and phytochrome photoreceptors. Downstream of these photoreceptors, asymmetric lateral redistribution of auxin underlies the differential growth, which results in phototropism. Historical physiological evidence and recent analysis of hormone-induced gene expression demonstrate that auxin and brassinosteroid signaling function interdependently. Similarly, in this study we report evidence that interactions between brassinosteroids and auxin signaling modulate phototropic responsiveness. We found that elongated, a previously identified photomorphogenesis mutant, enhances high-light phototropism and represents a unique allele of BAK1/SERK3, a receptor kinase implicated in brassinosteroid perception. Altogether, our results support the hypothesis that phototropic responsiveness is modulated by inputs that influence control of auxin response factor-mediated transcription.

  15. Molecular Genetic Analysis of Phototropism in Arabidopsis

    PubMed Central

    Sakai, Tatsuya; Haga, Ken

    2012-01-01

    Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes. PMID:22864452

  16. Molecular genetic analysis of phototropism in Arabidopsis.

    PubMed

    Sakai, Tatsuya; Haga, Ken

    2012-09-01

    Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes.

  17. A Brassinosteroid-Hypersensitive Mutant of BAK1 Indicates That a Convergence of Photomorphogenic and Hormonal Signaling Modulates Phototropism1

    PubMed Central

    Whippo, Craig W.; Hangarter, Roger P.

    2005-01-01

    The phototropic response of Arabidopsis (Arabidopsis thaliana) is induced by the phototropin photoreceptors and modulated by the cryptochrome and phytochrome photoreceptors. Downstream of these photoreceptors, asymmetric lateral redistribution of auxin underlies the differential growth, which results in phototropism. Historical physiological evidence and recent analysis of hormone-induced gene expression demonstrate that auxin and brassinosteroid signaling function interdependently. Similarly, in this study we report evidence that interactions between brassinosteroids and auxin signaling modulate phototropic responsiveness. We found that elongated, a previously identified photomorphogenesis mutant, enhances high-light phototropism and represents a unique allele of BAK1/SERK3, a receptor kinase implicated in brassinosteroid perception. Altogether, our results support the hypothesis that phototropic responsiveness is modulated by inputs that influence control of auxin response factor-mediated transcription. PMID:16126860

  18. Plasma membrane H+-ATPase regulation is required for auxin gradient formation preceding phototropic growth

    PubMed Central

    Hohm, Tim; Demarsy, Emilie; Quan, Clément; Allenbach Petrolati, Laure; Preuten, Tobias; Vernoux, Teva; Bergmann, Sven; Fankhauser, Christian

    2014-01-01

    Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H+-ATPases that are required to control apoplastic pH. Our results show that H+-ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H+-ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH. PMID:25261457

  19. Plant phototropic growth.

    PubMed

    Fankhauser, Christian; Christie, John M

    2015-05-04

    Plants are photoautotrophic sessile organisms that use environmental cues to optimize multiple facets of growth and development. A classic example is phototropism - in shoots this is typically positive, leading to growth towards the light, while roots frequently show negative phototropism triggering growth away from the light. Shoot phototropism optimizes light capture of leaves in low light environments and hence increases photosynthetic productivity. Phototropins are plasma-membrane-associated UV-A/blue-light activated kinases that trigger phototropic growth. Light perception liberates their protein kinase domain from the inhibitory action of the amino-terminal photosensory portion of the photoreceptor. Following a series of still poorly understood events, phototropin activation leads to the formation of a gradient of the growth hormone auxin across the photo-stimulated stem. The greater auxin concentration on the shaded compared with the lit side of the stem enables growth reorientation towards the light. In this Minireview, we briefly summarize the signaling steps starting from photoreceptor activation until the establishment of a lateral auxin gradient, ultimately leading to phototropic growth in shoots. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Arabidopsis ROOT PHOTOTROPISM2 Contributes to the Adaptation to High-Intensity Light in Phototropic Responses

    PubMed Central

    Haga, Ken; Tsuchida-Mayama, Tomoko; Yamada, Mizuki; Sakai, Tatsuya

    2015-01-01

    Living organisms adapt to changing light environments via mechanisms that enhance photosensitivity under darkness and attenuate photosensitivity under bright light conditions. In hypocotyl phototropism, phototropin1 (phot1) blue light photoreceptors mediate both the pulse light-induced, first positive phototropism and the continuous light-induced, second positive phototropism, suggesting the existence of a mechanism that alters their photosensitivity. Here, we show that light induction of ROOT PHOTOTROPISM2 (RPT2) underlies photosensory adaptation in hypocotyl phototropism of Arabidopsis thaliana. rpt2 loss-of-function mutants exhibited increased photosensitivity to very low fluence blue light but were insensitive to low fluence blue light. Expression of RPT2 prior to phototropic stimulation in etiolated seedlings reduced photosensitivity during first positive phototropism and accelerated second positive phototropism. Our microscopy and biochemical analyses indicated that blue light irradiation causes dephosphorylation of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) proteins and mediates their release from the plasma membrane. These phenomena correlate closely with the desensitization of phot1 signaling during the transition period from first positive phototropism to second positive phototropism. RPT2 modulated the phosphorylation of NPH3 and promoted reconstruction of the phot1-NPH3 complex on the plasma membrane. We conclude that photosensitivity is increased in the absence of RPT2 and that this results in the desensitization of phot1. Light-mediated induction of RPT2 then reduces the photosensitivity of phot1, which is required for second positive phototropism under bright light conditions. PMID:25873385

  1. REPRESSOR OF ULTRAVIOLET-B PHOTOMORPHOGENESIS function allows efficient phototropin mediated ultraviolet-B phototropism in etiolated seedlings.

    PubMed

    Vanhaelewyn, Lucas; Schumacher, Paolo; Poelman, Dirk; Fankhauser, Christian; Van Der Straeten, Dominique; Vandenbussche, Filip

    2016-11-01

    Ultraviolet B (UV-B) light is a part of the solar radiation which has significant effects on plant morphology, even at low doses. In Arabidopsis, many of these morphological changes have been attributed to a specific UV-B receptor, UV resistance locus 8 (UVR8). Recent findings showed that next to phototropin regulated phototropism, UVR8 mediated signaling is able of inducing directional bending towards UV-B light in etiolated seedlings of Arabidopsis, in a phototropin independent manner. In this study, kinetic analysis of phototropic bending was used to evaluate the relative contribution of each of these pathways in UV-B mediated phototropism. Diminishing UV-B light intensity favors the importance of phototropins. Molecular and genetic analyses suggest that UV-B is capable of inducing phototropin signaling relying on phototropin kinase activity and regulation of NPH3. Moreover, enhanced UVR8 responses in the UV-B hypersensitive rup1rup2 mutants interferes with the fast phototropin mediated phototropism. Together the data suggest that phototropins are the most important receptors for UV-B induced phototropism in etiolated seedlings, and a RUP mediated negative feedback pathway prevents UVR8 signaling to interfere with the phototropin dependent response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Phototropin and light-signaling in phototropism.

    PubMed

    Kimura, Mitsuhiro; Kagawa, Takatoshi

    2006-10-01

    Blue-light-induced phototropism in higher plants is regulated by phototropin, which is a photoreceptor kinase that contains a flavin mononucleotide (FMN). Recently, it was found that this kinase is inhibited by the binding of the LOV2 (light-oxygen-voltage2) domain in the dark but that its activity is increased in the light by the release of the LOV2 domain. Phototropin-associated proteins have been identified, although the proteins that are phosphorylated by phototropin are still unknown. The asymmetrical auxin distribution caused by unilateral irradiation suggests that differential growth is induced by a difference in auxin-regulated gene expression between the shaded and illuminated sides of plant organs. Transcription-related factors, such as NPH4/ARF7, MSG2/IAA19 and SCF(TIR1), play key roles in this process.

  3. Clathrin regulates blue light-triggered lateral auxin distribution and hypocotyl phototropism in Arabidopsis.

    PubMed

    Zhang, Ying; Yu, Qinqin; Jiang, Nan; Yan, Xu; Wang, Chao; Wang, Qingmei; Liu, Jianzhong; Zhu, Muyuan; Bednarek, Sebastian Y; Xu, Jian; Pan, Jianwei

    2017-01-01

    Phototropism is the process by which plants grow towards light in order to maximize the capture of light for photosynthesis, which is particularly important for germinating seedlings. In Arabidopsis, hypocotyl phototropism is predominantly triggered by blue light (BL), which has a profound effect on the establishment of asymmetric auxin distribution, essential for hypocotyl phototropism. Two auxin efflux transporters ATP-binding cassette B19 (ABCB19) and PIN-formed 3 (PIN3) are known to mediate the effect of BL on auxin distribution in the hypocotyl, but the details for how BL triggers PIN3 lateralization remain poorly understood. Here, we report a critical role for clathrin in BL-triggered, PIN3-mediated asymmetric auxin distribution in hypocotyl phototropism. We show that unilateral BL induces relocalization of clathrin in the hypocotyl. Loss of clathrin light chain 2 (CLC2) and CLC3 affects endocytosis and lateral distribution of PIN3 thereby impairing BL-triggered establishment of asymmetric auxin distribution and consequently, phototropic bending. Conversely, auxin efflux inhibitors N-1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid affect BL-induced relocalization of clathrin, endocytosis and lateralization of PIN3 as well as asymmetric distribution of auxin. These results together demonstrate an important interplay between auxin and clathrin function that dynamically regulates BL-triggered hypocotyl phototropism in Arabidopsis. © 2016 John Wiley & Sons Ltd.

  4. Arabidopsis ROOT PHOTOTROPISM2 Contributes to the Adaptation to High-Intensity Light in Phototropic Responses.

    PubMed

    Haga, Ken; Tsuchida-Mayama, Tomoko; Yamada, Mizuki; Sakai, Tatsuya

    2015-04-01

    Living organisms adapt to changing light environments via mechanisms that enhance photosensitivity under darkness and attenuate photosensitivity under bright light conditions. In hypocotyl phototropism, phototropin1 (phot1) blue light photoreceptors mediate both the pulse light-induced, first positive phototropism and the continuous light-induced, second positive phototropism, suggesting the existence of a mechanism that alters their photosensitivity. Here, we show that light induction of ROOT PHOTOTROPISM2 (RPT2) underlies photosensory adaptation in hypocotyl phototropism of Arabidopsis thaliana. rpt2 loss-of-function mutants exhibited increased photosensitivity to very low fluence blue light but were insensitive to low fluence blue light. Expression of RPT2 prior to phototropic stimulation in etiolated seedlings reduced photosensitivity during first positive phototropism and accelerated second positive phototropism. Our microscopy and biochemical analyses indicated that blue light irradiation causes dephosphorylation of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) proteins and mediates their release from the plasma membrane. These phenomena correlate closely with the desensitization of phot1 signaling during the transition period from first positive phototropism to second positive phototropism. RPT2 modulated the phosphorylation of NPH3 and promoted reconstruction of the phot1-NPH3 complex on the plasma membrane. We conclude that photosensitivity is increased in the absence of RPT2 and that this results in the desensitization of phot1. Light-mediated induction of RPT2 then reduces the photosensitivity of phot1, which is required for second positive phototropism under bright light conditions. © 2015 American Society of Plant Biologists. All rights reserved.

  5. Plasma membrane H⁺ -ATPase regulation is required for auxin gradient formation preceding phototropic growth.

    PubMed

    Hohm, Tim; Demarsy, Emilie; Quan, Clément; Allenbach Petrolati, Laure; Preuten, Tobias; Vernoux, Teva; Bergmann, Sven; Fankhauser, Christian

    2014-09-26

    Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H⁺ -ATPases that are required to control apoplastic pH. Our results show that H⁺ -ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H⁺ -ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  6. PHYTOCHROME KINASE SUBSTRATE1 Regulates Root Phototropism and Gravitropism1[C][W][OA

    PubMed Central

    Boccalandro, Hernán E.; De Simone, Silvia N.; Bergmann-Honsberger, Ariane; Schepens, Isabelle; Fankhauser, Christian; Casal, Jorge J.

    2008-01-01

    Light promotes the expression of PHYTOCHROME KINASE SUBSTRATE1 (PKS1) in the root of Arabidopsis thaliana, but the function of PKS1 in this organ is unknown. Unilateral blue light induced a negative root phototropic response mediated by phototropin 1 in wild-type seedlings. This response was absent in pks1 mutants. In the wild type, unilateral blue light enhanced PKS1 expression in the subapical region of the root several hours before bending was detectable. The negative phototropism and the enhanced PKS1 expression in response to blue light required phytochrome A (phyA). In addition, the pks1 mutation enhanced the root gravitropic response when vertically oriented seedlings were placed horizontally. The negative regulation of gravitropism by PKS1 occurred even in dark-grown seedlings and did not require phyA. Blue light also failed to induce negative phototropism in pks1 under reduced gravitational stimulation, indicating that the effect of pks1 on phototropism is not simply the consequence of the counteracting effect of enhanced gravitropism. We propose a model where the background level of PKS1 reduces gravitropism. After a phyA-dependent increase in its expression, PKS1 positively affects root phototropism and both effects contribute to negative curvature in response to unilateral blue light. PMID:18024556

  7. Light-induced phosphorylation of a membrane protein plays an early role in signal transduction for phototropism in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Reymond, P.; Short, T. W.; Briggs, W. R.; Poff, K. L.

    1992-01-01

    Blue light is known to cause rapid phosphorylation of a membrane protein in etiolated seedlings of several plant species, a protein that, at least in etiolated pea seedlings and maize coleoptiles, has been shown to be associated with the plasma membrane. The light-driven phosphorylation has been proposed on the basis of correlative evidence to be an early step in the signal transduction chain for phototropism. In the Arabidopsis thaliana mutant JK224, the sensitivity to blue light for induction of first positive phototropism is known to be 20- to 30-fold lower than in wild type, whereas second positive curvature appears to be normal. While light-induced phosphorylation can be demonstrated in crude membrane preparations from shoots of the mutant, the level of phosphorylation is dramatically lower than in wild type, as is the sensitivity to blue light. Another A. thaliana mutant, JK218, that completely lacks any phototropic responses to up to 2 h of irradiation, shows a normal level of light-induced phosphorylation at saturation. Since its gravitropic sensitivity is normal, it is presumably blocked in some step between photoreception and the confluence of the signal transduction pathways for phototropism and gravitropism. We conclude from mutant JK224 that light-induced phosphorylation plays an early role in the signal transduction chain for phototropism in higher plants.

  8. Second positive phototropism results from coordinated co-action of the phototropins and cryptochromes.

    PubMed

    Whippo, Craig W; Hangarter, Roger P

    2003-07-01

    Phototropism and hypocotyl growth inhibition are modulated by the coaction of different blue-light photoreceptors and their signaling pathways. How seedlings integrate the activities of the different blue-light photoreceptors to coordinate these hypocotyl growth responses is still unclear. We have used time-lapse imaging and a nontraditional mathematical approach to conduct a detailed examination of phototropism in wild-type Arabidopsis and various blue-light photoreceptor mutants. Our results indicate that high fluence rates of blue light (100 micro mol m(-)(2) s(-)(1)) attenuate phototropism through the coaction of the phototropin and cryptochrome blue-light photoreceptors. In contrast, we also demonstrate that phototropins and cryptochromes function together to enhance phototropism under low fluence rates (<1.0 micro mol m(-)(2) s(-)(1)) of blue light. Based on our results, we hypothesize that phototropins and cryptochromes regulate phototropism by coordinating the balance between stimulation and inhibition of growth of the hypocotyl depending on the fluence rate of blue light.

  9. PINOID AGC kinases are necessary for phytochrome-mediated enhancement of hypocotyl phototropism in Arabidopsis.

    PubMed

    Haga, Ken; Hayashi, Ken-ichiro; Sakai, Tatsuya

    2014-11-01

    Several members of the AGCVIII kinase subfamily, which includes PINOID (PID), PID2, and WAVY ROOT GROWTH (WAG) proteins, have previously been shown to phosphorylate PIN-FORMED (PIN) auxin transporters and control the auxin flow in plants. PID has been proposed as a key component of the phototropin signaling pathway that induces phototropic responses, although the responses were not significantly impaired in the pid single and pid wag1 wag2 triple mutants. This raises questions about the functional roles of the PID family in phototropic responses. Here, we investigated hypocotyl phototropism in the pid pid2 wag1 wag2 quadruple mutant in detail to clarify the roles of the PID family in Arabidopsis (Arabidopsis thaliana). The pid quadruple mutants exhibited moderate responses in continuous light-induced phototropism with a decrease in growth rates of hypocotyls and normal responses in pulse-induced phototropism. However, they showed serious defects in enhancements of pulse-induced phototropic curvatures and lateral fluorescent auxin transport by red light pretreatment. Red light pretreatment significantly reduced the expression level of PID, and the constitutive expression of PID prevented pulse-induced phototropism, irrespective of red light pretreatment. This suggests that the PID family plays a significant role in phytochrome-mediated phototropic enhancement but not the phototropin signaling pathway. Red light treatment enhanced the intracellular accumulation of PIN proteins in response to the vesicle-trafficking inhibitor brefeldin A in addition to increasing their expression levels. Taken together, these results suggest that red light preirradiation enhances phototropic curvatures by up-regulation of PIN proteins, which are not being phosphorylated by the PID family. © 2014 American Society of Plant Biologists. All Rights Reserved.

  10. Phytochromes A and B mediate red-light-induced positive phototropism in roots

    NASA Technical Reports Server (NTRS)

    Kiss, John Z.; Mullen, Jack L.; Correll, Melanie J.; Hangarter, Roger P.

    2003-01-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30 degrees to 40 degrees, compared with 5 degrees to 10 degrees without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants.

  11. Phytochromes A and B mediate red-light-induced positive phototropism in roots.

    PubMed

    Kiss, John Z; Mullen, Jack L; Correll, Melanie J; Hangarter, Roger P

    2003-03-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30 degrees to 40 degrees, compared with 5 degrees to 10 degrees without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants.

  12. Second Positive Phototropism Results from Coordinated Co-Action of the Phototropins and Cryptochromes1

    PubMed Central

    Whippo, Craig W.; Hangarter, Roger P.

    2003-01-01

    Phototropism and hypocotyl growth inhibition are modulated by the coaction of different blue-light photoreceptors and their signaling pathways. How seedlings integrate the activities of the different blue-light photoreceptors to coordinate these hypocotyl growth responses is still unclear. We have used time-lapse imaging and a nontraditional mathematical approach to conduct a detailed examination of phototropism in wild-type Arabidopsis and various blue-light photoreceptor mutants. Our results indicate that high fluence rates of blue light (100 μmol m–2 s–1) attenuate phototropism through the coaction of the phototropin and cryptochrome blue-light photoreceptors. In contrast, we also demonstrate that phototropins and cryptochromes function together to enhance phototropism under low fluence rates (<1.0 μmol m–2 s–1) of blue light. Based on our results, we hypothesize that phototropins and cryptochromes regulate phototropism by coordinating the balance between stimulation and inhibition of growth of the hypocotyl depending on the fluence rate of blue light. PMID:12857830

  13. Phytochromes A and B Mediate Red-Light-Induced Positive Phototropism in Roots1

    PubMed Central

    Kiss, John Z.; Mullen, Jack L.; Correll, Melanie J.; Hangarter, Roger P.

    2003-01-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30° to 40°, compared with 5° to 10° without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants. PMID:12644690

  14. Twilight, a Novel Circadian-Regulated Gene, Integrates Phototropism with Nutrient and Redox Homeostasis during Fungal Development

    PubMed Central

    Naqvi, Naweed I.

    2015-01-01

    Phototropic regulation of circadian clock is important for environmental adaptation, organismal growth and differentiation. Light plays a critical role in fungal development and virulence. However, it is unclear what governs the intracellular metabolic response to such dark-light rhythms in fungi. Here, we describe a novel circadian-regulated Twilight (TWL) function essential for phototropic induction of asexual development and pathogenesis in the rice-blast fungus Magnaporthe oryzae. The TWL transcript oscillates during circadian cycles and peaks at subjective twilight. GFP-Twl remains acetylated and cytosolic in the dark, whereas light-induced phosphorylation (by the carbon sensor Snf1 kinase) drives it into the nucleus. The mRNA level of the transcription/repair factor TFB5, was significantly down regulated in the twl∆ mutant. Overexpression of TFB5 significantly suppressed the conidiation defects in the twl∆ mutant. Furthermore, Tfb5-GFP translocates to the nucleus during the phototropic response and under redox stress, while it failed to do so in the twl∆ mutant. Thus, we provide mechanistic insight into Twl-based regulation of nutrient and redox homeostasis in response to light during pathogen adaptation to the host milieu in the rice blast pathosystem. PMID:26102503

  15. Twilight, a Novel Circadian-Regulated Gene, Integrates Phototropism with Nutrient and Redox Homeostasis during Fungal Development.

    PubMed

    Deng, Yi Zhen; Qu, Ziwei; Naqvi, Naweed I

    2015-06-01

    Phototropic regulation of circadian clock is important for environmental adaptation, organismal growth and differentiation. Light plays a critical role in fungal development and virulence. However, it is unclear what governs the intracellular metabolic response to such dark-light rhythms in fungi. Here, we describe a novel circadian-regulated Twilight (TWL) function essential for phototropic induction of asexual development and pathogenesis in the rice-blast fungus Magnaporthe oryzae. The TWL transcript oscillates during circadian cycles and peaks at subjective twilight. GFP-Twl remains acetylated and cytosolic in the dark, whereas light-induced phosphorylation (by the carbon sensor Snf1 kinase) drives it into the nucleus. The mRNA level of the transcription/repair factor TFB5, was significantly down regulated in the twl∆ mutant. Overexpression of TFB5 significantly suppressed the conidiation defects in the twl∆ mutant. Furthermore, Tfb5-GFP translocates to the nucleus during the phototropic response and under redox stress, while it failed to do so in the twl∆ mutant. Thus, we provide mechanistic insight into Twl-based regulation of nutrient and redox homeostasis in response to light during pathogen adaptation to the host milieu in the rice blast pathosystem.

  16. Negative phototropism is seen in Arabidopsis inflorescences when auxin signaling is reduced to a minimal level by an Aux/IAA dominant mutation, axr2.

    PubMed

    Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T

    2015-01-01

    Inflorescences of a dominant mutant of Arabidopsis Aux/IAA7, axr2, showed negative phototropism with a similar fluence response curve to the positive phototropism of wild-type stems. Application of a synthetic auxin, NAA, and an inhibitor of polar auxin transport, NPA, increased and decreased respectively the magnitude of the phototropic response in the wild type, while in axr2 application of NAA reduced the negative phototropic response and NPA had no effect. Decapitation of the apex induced a small negative phototropism in wild-type stems, and had no effect in axr2 plants. Inflorescences of the double mutants of auxin transporters, pgp1 pgp19, showed no phototropic response, while decapitation resulted in a negative phototropic response. These results suggest that negative phototropism can occur when the level of auxin or of auxin signaling is reduced to a minimal level, and that in plant axial organs the default phototropic response to unilateral blue light may be negative. Expression of axr2 protein by an endodermis-specific promoter resulted in agravitropism of inflorescences in a similar way to that of axr2, but phototropism was normal, confirming that the endodermis does not play a critical role in phototropism.

  17. Negative phototropism is seen in Arabidopsis inflorescences when auxin signaling is reduced to a minimal level by an Aux/IAA dominant mutation, axr2

    PubMed Central

    Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T.

    2015-01-01

    Inflorescences of a dominant mutant of Arabidopsis Aux/IAA7, axr2, showed negative phototropism with a similar fluence response curve to the positive phototropism of wild-type stems. Application of a synthetic auxin, NAA, and an inhibitor of polar auxin transport, NPA, increased and decreased respectively the magnitude of the phototropic response in the wild type, while in axr2 application of NAA reduced the negative phototropic response and NPA had no effect. Decapitation of the apex induced a small negative phototropism in wild-type stems, and had no effect in axr2 plants. Inflorescences of the double mutants of auxin transporters, pgp1 pgp19, showed no phototropic response, while decapitation resulted in a negative phototropic response. These results suggest that negative phototropism can occur when the level of auxin or of auxin signaling is reduced to a minimal level, and that in plant axial organs the default phototropic response to unilateral blue light may be negative. Expression of axr2 protein by an endodermis-specific promoter resulted in agravitropism of inflorescences in a similar way to that of axr2, but phototropism was normal, confirming that the endodermis does not play a critical role in phototropism. PMID:25738325

  18. Phototropism in gametophytic shoots of the moss Physcomitrella patens.

    PubMed

    Bao, Liang; Yamamoto, Kotaro T; Fujita, Tomomichi

    2015-01-01

    Shoot phototropism enables plants to position their photosynthetic organs in favorable light conditions and thus benefits growth and metabolism in land plants. To understand the evolution of this response, we established an experimental system to study phototropism in gametophores of the moss Physcomitrella patens. The phototropic response of gametophores occurs slowly; a clear response takes place more than 24 hours after the onset of unilateral light irradiation, likely due to the slow growth rate of gametophores. We also found that red and far-red light can induce phototropism, with blue light being less effective. These results suggest that plants used a broad range of light wavelengths as phototropic signals during the early evolution of land plants.

  19. Phototropism in gametophytic shoots of the moss Physcomitrella patens

    PubMed Central

    Bao, Liang; Yamamoto, Kotaro T; Fujita, Tomomichi

    2015-01-01

    Shoot phototropism enables plants to position their photosynthetic organs in favorable light conditions and thus benefits growth and metabolism in land plants. To understand the evolution of this response, we established an experimental system to study phototropism in gametophores of the moss Physcomitrella patens. The phototropic response of gametophores occurs slowly; a clear response takes place more than 24 hours after the onset of unilateral light irradiation, likely due to the slow growth rate of gametophores. We also found that red and far-red light can induce phototropism, with blue light being less effective. These results suggest that plants used a broad range of light wavelengths as phototropic signals during the early evolution of land plants. PMID:25848889

  20. PINOID AGC Kinases Are Necessary for Phytochrome-Mediated Enhancement of Hypocotyl Phototropism in Arabidopsis1[W][OPEN

    PubMed Central

    Haga, Ken; Hayashi, Ken-ichiro; Sakai, Tatsuya

    2014-01-01

    Several members of the AGCVIII kinase subfamily, which includes PINOID (PID), PID2, and WAVY ROOT GROWTH (WAG) proteins, have previously been shown to phosphorylate PIN-FORMED (PIN) auxin transporters and control the auxin flow in plants. PID has been proposed as a key component of the phototropin signaling pathway that induces phototropic responses, although the responses were not significantly impaired in the pid single and pid wag1 wag2 triple mutants. This raises questions about the functional roles of the PID family in phototropic responses. Here, we investigated hypocotyl phototropism in the pid pid2 wag1 wag2 quadruple mutant in detail to clarify the roles of the PID family in Arabidopsis (Arabidopsis thaliana). The pid quadruple mutants exhibited moderate responses in continuous light-induced phototropism with a decrease in growth rates of hypocotyls and normal responses in pulse-induced phototropism. However, they showed serious defects in enhancements of pulse-induced phototropic curvatures and lateral fluorescent auxin transport by red light pretreatment. Red light pretreatment significantly reduced the expression level of PID, and the constitutive expression of PID prevented pulse-induced phototropism, irrespective of red light pretreatment. This suggests that the PID family plays a significant role in phytochrome-mediated phototropic enhancement but not the phototropin signaling pathway. Red light treatment enhanced the intracellular accumulation of PIN proteins in response to the vesicle-trafficking inhibitor brefeldin A in addition to increasing their expression levels. Taken together, these results suggest that red light preirradiation enhances phototropic curvatures by up-regulation of PIN proteins, which are not being phosphorylated by the PID family. PMID:25281709

  1. Chemistry and biology of phototropism-regulating substances in higher plants.

    PubMed

    Yamamura, S; Hasegawa, K

    2001-01-01

    Most people are familiar with the sight of a young seedling bending towards a window or the brightest source of light to which it is exposed. This directional growth response is known as phototropism, which is caused by a lateral growth-promoting auxin in the bending organ (Cholodny-Went theory, cited in high school textbook). Recently, however, Bruinsma et al., Weiler et al., and Hasegawa et al. independently found that the shaded half did not contain more auxin than the illuminated one. Instead it was found that the even distribution of auxin was accompanied by a lateral gradient of growth inhibiting substances during phototropic curvature (Bruinsma-Hasegawa theory). We have isolated some photo-induced growth inhibitory substances related to phototropism, benzoxazolinones from light-grown maize shoots (Zea mays L.), raphanusanins from radish hypocotyl (Raphanus sativus var. hortensis f. gigantissimus M.), indolyacetonitrile from light-grown shoots (Brassica oleacea L.), 8-epixanthatin from sunflower hypocotyl (Helianthus annus L.), and quite recently uridine from oat coleoptile (Avena sativa L.). Chemical analyses have shown phototropic stimulations to cause curvature by inducing a local unequal distribution of growth-inhibiting substances that antagonize auxin in its cell-elongating activity. Finally, a model is presented for further studies on phototropism. Copyright 2001 The Japan Chemical Journal Forum and John Wiley & Sons, Inc.

  2. Phytochrome mediates red-light-based positive phototropism in Arabidopsis roots

    NASA Astrophysics Data System (ADS)

    Correll, M.; Mullen, J.; Hangarter, R.; Kiss, J.

    Plants rely on sophisticated mechanisms to interpret the constant bombardment of incoming signals so they can adjust their growth accordingly. The environmental cues of gravity and light are particularly important for plant growth and development. While gravitropism has been extensively studied in roots, there has been increased emphasis on understanding the cellular and molecular basis of root phototropism. In addition to the blue-light-based negative phototropism, roots also exhibit a recently discovered positive phototropism in response to red light. In this paper, we characterize this red-light-based phototropism in roots of Arabidopsis.

  3. Asymmetric Auxin Distribution is Not Required to Establish Root Phototropism in Arabidopsis.

    PubMed

    Kimura, Taro; Haga, Ken; Shimizu-Mitao, Yasushi; Takebayashi, Yumiko; Kasahara, Hiroyuki; Hayashi, Ken-Ichiro; Kakimoto, Tatsuo; Sakai, Tatsuya

    2018-04-01

    An asymmetric auxin distribution pattern is assumed to underlie the tropic responses of seed plants. It is unclear, however, whether this pattern is required for root negative phototropism. We here demonstrate that asymmetric auxin distribution is not required to establish root phototropism in Arabidopsis. Our detailed analyses of auxin reporter genes indicate that auxin accumulates on the irradiated side of roots in response to an incidental gravitropic stimulus caused by phototropic bending. Further, an agravitropic mutant showed a suppression of this accumulation with an enhancement of the phototropic response. In this context, our pharmacological and genetic analyses revealed that both polar auxin transport and auxin biosynthesis are critical for the establishment of root gravitropism, but not for root phototropism, and that defects in these processes actually enhance phototropic responses in roots. The auxin response factor double mutant arf7 arf19 and the auxin receptor mutant tir1 showed a slight reduction in phototropic curvatures in roots, suggesting that the transcriptional regulation by some specific ARF proteins and their regulators is at least partly involved in root phototropism. However, the auxin antagonist PEO-IAA [α-(phenylethyl-2-one)-indole-3-acetic acid] suppressed root gravitropism and enhanced root phototropism, suggesting that the TIR1/AFB auxin receptors and ARF transcriptional factors play minor roles in root phototropism. Taken together, we conclude from our current data that the phototropic response in Arabidopsis roots is induced by an unknown mechanism that does not require asymmetric auxin distribution and that the Cholodny-Went hypothesis probably does not apply to root phototropism.

  4. Roles of AGCVIII Kinases in the Hypocotyl Phototropism of Arabidopsis Seedlings.

    PubMed

    Haga, Ken; Frank, Lena; Kimura, Taro; Schwechheimer, Claus; Sakai, Tatsuya

    2018-05-01

    Regulation of protein function by phosphorylation and dephosphorylation is an important mechanism in many cellular events. The phototropin blue-light photoreceptors, plant-specific AGCVIII kinases, are essential for phototropic responses. Members of the D6 PROTEIN KINASE (D6PK) family, representing a subfamily of the AGCVIII kinases, also contribute to phototropic responses, suggesting that possibly further AGCVIII kinases may potentially control phototropism. The present study investigates the functional roles of Arabidopsis (Arabidopsis thaliana) AGCVIII kinases in hypocotyl phototropism. We demonstrate that D6PK family kinases are not only required for the second but also for the first positive phototropism. In addition, we find that a previously uncharacterized AGCVIII protein, AGC1-12, is involved in the first positive phototropism and gravitropism. AGC1-12 phosphorylates serine residues in the cytoplasmic loop of PIN-FORMED 1 (PIN1) and shares phosphosite preferences with D6PK. Our work strongly suggests that the D6PK family and AGC1-12 are critical components for both hypocotyl phototropism and gravitropism, and that these kinases control tropic responses mainly through regulation of PIN-mediated auxin transport by protein phosphorylation.

  5. Reduced phototropism in pks mutants may be due to altered auxin-regulated gene expression or reduced lateral auxin transport.

    PubMed

    Kami, Chitose; Allenbach, Laure; Zourelidou, Melina; Ljung, Karin; Schütz, Frédéric; Isono, Erika; Watahiki, Masaaki K; Yamamoto, Kotaro T; Schwechheimer, Claus; Fankhauser, Christian

    2014-02-01

    Phototropism allows plants to orient their photosynthetic organs towards the light. In Arabidopsis, phototropins 1 and 2 sense directional blue light such that phot1 triggers phototropism in response to low fluence rates, while both phot1 and phot2 mediate this response under higher light conditions. Phototropism results from asymmetric growth in the hypocotyl elongation zone that depends on an auxin gradient across the embryonic stem. How phototropin activation leads to this growth response is still poorly understood. Members of the phytochrome kinase substrate (PKS) family may act early in this pathway, because PKS1, PKS2 and PKS4 are needed for a normal phototropic response and they associate with phot1 in vivo. Here we show that PKS proteins are needed both for phot1- and phot2-mediated phototropism. The phototropic response is conditioned by the developmental asymmetry of dicotyledonous seedlings, such that there is a faster growth reorientation when cotyledons face away from the light compared with seedlings whose cotyledons face the light. The molecular basis for this developmental effect on phototropism is unknown; here we show that PKS proteins play a role at the interface between development and phototropism. Moreover, we present evidence for a role of PKS genes in hypocotyl gravi-reorientation that is independent of photoreceptors. pks mutants have normal levels of auxin and normal polar auxin transport, however they show altered expression patterns of auxin marker genes. This situation suggests that PKS proteins are involved in auxin signaling and/or lateral auxin redistribution. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  6. PIN auxin efflux carriers are necessary for pulse-induced but not continuous light-induced phototropism in Arabidopsis.

    PubMed

    Haga, Ken; Sakai, Tatsuya

    2012-10-01

    Auxin efflux carrier PIN-FORMED (PIN) proteins are thought to have central roles in regulating asymmetrical auxin translocation during tropic responses, including gravitropism and phototropism, in plants. Although PIN3 is known to be involved in phototropism in Arabidopsis (Arabidopsis thaliana), no severe defects of phototropism in any of the pin mutants have been reported. We show here that the pulse-induced, first positive phototropism is impaired partially in pin1, pin3, and pin7 single mutants, and severely in triple mutants. In contrast, such impairment was not observed in continuous-light-induced second positive phototropism. Analysis with an auxin-reporter gene demonstrated that PIN3-mediated auxin gradients participate in pulse-induced phototropism but not in continuous-light-induced phototropism. Similar functional separation was also applicable to PINOID, a regulator of PIN localization. Our results strongly suggest the existence of functionally distinct mechanisms i.e. a PIN-dependent mechanism in which transient stimulation is sufficient to induce phototropism, and a PIN-independent mechanism that requires continuous stimulation and does not operate in the former phototropism process. Although a previous study has proposed that blue-light photoreceptors, the phototropins, control PIN localization through the transcriptional down-regulation of PINOID, we could not detect this blue-light-dependent down-regulation event, suggesting that other as yet unknown mechanisms are involved in phototropin-mediated phototropic responses.

  7. The Rice COLEOPTILE PHOTOTROPISM1 gene encoding an ortholog of Arabidopsis NPH3 is required for phototropism of coleoptiles and lateral translocation of auxin.

    PubMed

    Haga, Ken; Takano, Makoto; Neumann, Ralf; Iino, Moritoshi

    2005-01-01

    We isolated a mutant, named coleoptile phototropism1 (cpt1), from gamma-ray-mutagenized japonica-type rice (Oryza sativa). This mutant showed no coleoptile phototropism and severely reduced root phototropism after continuous stimulation. A map-based cloning strategy and transgenic complementation test were applied to demonstrate that a NPH3-like gene deleted in the mutant corresponds to CPT1. Phylogenetic analysis of putative CPT1 homologs of rice and related proteins indicated that CPT1 has an orthologous relationship with Arabidopsis thaliana NPH3. These results, along with those for Arabidopsis, demonstrate that NPH3/CPT1 is a key signal transduction component of higher plant phototropism. In an extended study with the cpt1 mutant, it was found that phototropic differential growth is accompanied by a CPT1-independent inhibition of net growth. Kinetic investigation further indicated that a small phototropism occurs in cpt1 coleoptiles. This response, induced only transiently, was thought to be caused by the CPT1-independent growth inhibition. The 3H-indole-3-acetic acid applied to the coleoptile tip was asymmetrically distributed between the two sides of phototropically responding coleoptiles. However, no asymmetry was induced in cpt1 coleoptiles, indicating that lateral translocation of auxin occurs downstream of CPT1. It is concluded that the CPT1-dependent major phototropism of coleoptiles is achieved by lateral auxin translocation and subsequent growth redistribution.

  8. Phototropins function in high-intensity blue light-induced hypocotyl phototropism in Arabidopsis by altering cytosolic calcium.

    PubMed

    Zhao, Xiang; Wang, Yan-Liang; Qiao, Xin-Rong; Wang, Jin; Wang, Lin-Dan; Xu, Chang-Shui; Zhang, Xiao

    2013-07-01

    Phototropins (phot1 and phot2), the blue light receptors in plants, regulate hypocotyl phototropism in a fluence-dependent manner. Especially under high fluence rates of blue light (HBL), the redundant function mediated by both phot1 and phot2 drastically restricts the understanding of the roles of phot2. Here, systematic analysis of phototropin-related mutants and overexpression transgenic lines revealed that HBL specifically induced a transient increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in Arabidopsis (Arabidopsis thaliana) hypocotyls and that the increase in [Ca(2+)]cyt was primarily attributed to phot2. Pharmacological and genetic experiments illustrated that HBL-induced Ca(2+) increases were modulated differently by phot1 and phot2. Phot2 mediated the HBL-induced increase in [Ca(2+)]cyt mainly by an inner store-dependent Ca(2+)-release pathway, not by activating plasma membrane Ca(2+) channels. Further analysis showed that the increase in [Ca(2+)]cyt was possibly responsible for HBL-induced hypocotyl phototropism. An inhibitor of auxin efflux carrier exhibited significant inhibitions of both phototropism and increases in [Ca(2+)]cyt, which indicates that polar auxin transport is possibly involved in HBL-induced responses. Moreover, PHYTOCHROME KINASE SUBSTRATE1 (PKS1), the phototropin-related signaling element identified, interacted physically with phototropins, auxin efflux carrier PIN-FORMED1 and calcium-binding protein CALMODULIN4, in vitro and in vivo, respectively, and HBL-induced phototropism was impaired in pks multiple mutants, indicating the role of the PKS family in HBL-induced phototropism. Together, these results provide new insights into the functions of phototropins and highlight a potential integration point through which Ca(2+) signaling-related HBL modulates hypocotyl phototropic responses.

  9. PHYTOCHROME KINASE SUBSTRATE 1 is a phototropin 1 binding protein required for phototropism.

    PubMed

    Lariguet, Patricia; Schepens, Isabelle; Hodgson, Daniel; Pedmale, Ullas V; Trevisan, Martine; Kami, Chitose; de Carbonnel, Matthieu; Alonso, José M; Ecker, Joseph R; Liscum, Emmanuel; Fankhauser, Christian

    2006-06-27

    Phototropism, or plant growth in response to unidirectional light, is an adaptive response of crucial importance. Lateral differences in low fluence rates of blue light are detected by phototropin 1 (phot1) in Arabidopsis. Only NONPHOTOTROPIC HYPOCOTYL 3 (NPH3) and root phototropism 2, both belonging to the same family of proteins, have been previously identified as phototropin-interacting signal transducers involved in phototropism. PHYTOCHROME KINASE SUBSTRATE (PKS) 1 and PKS2 are two phytochrome signaling components belonging to a small gene family in Arabidopsis (PKS1-PKS4). The strong enhancement of PKS1 expression by blue light and its light induction in the elongation zone of the hypocotyl prompted us to study the function of this gene family during phototropism. Photobiological experiments show that the PKS proteins are critical for hypocotyl phototropism. Furthermore, PKS1 interacts with phot1 and NPH3 in vivo at the plasma membrane and in vitro, indicating that the PKS proteins may function directly with phot1 and NPH3 to mediate phototropism. The phytochromes are known to influence phototropism but the mechanism involved is still unclear. We show that PKS1 induction by a pulse of blue light is phytochrome A-dependent, suggesting that the PKS proteins may provide a molecular link between these two photoreceptor families.

  10. GNOM regulates root hydrotropism and phototropism independently of PIN-mediated auxin transport.

    PubMed

    Moriwaki, Teppei; Miyazawa, Yutaka; Fujii, Nobuharu; Takahashi, Hideyuki

    2014-02-01

    Plant roots exhibit tropisms in response to gravity, unilateral light and moisture gradients. During gravitropism, an auxin gradient is established by PIN auxin transporters, leading to asymmetric growth. GNOM, a guanine nucleotide exchange factor of ARF GTPase (ARF-GEF), regulates PIN localization by regulating subcellular trafficking of PINs. Therefore, GNOM is important for gravitropism. We previously isolated mizu-kussei2 (miz2), which lacks hydrotropic responses; MIZ2 is allelic to GNOM. Since PIN proteins are not required for root hydrotropism in Arabidopsis, the role of GNOM in root hydrotropism should differ from that in gravitropism. To examine this possibility, we conducted genetic analysis of gnom(miz2) and gnom trans-heterozygotes. The mutant gnom(miz2), which lacks hydrotropic responses, was partially recovered by gnom(emb30-1), which lacks GEF activity, but not by gnom(B4049), which lacks heterotypic domain interactions. Furthermore, the phototropic response of gnom trans-heterozygotes differed from that of the pin2 mutant allele eir1-1. Moreover, defects in the polarities of PIN2 and auxin distribution in a severe gnom mutant were recovered by gnom(miz2). Therefore, an unknown GNOM-mediated vesicle trafficking system may mediate root hydrotropism and phototropism independently of PIN trafficking. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. PHYTOCHROME KINASE SUBSTRATE 1 is a phototropin 1 binding protein required for phototropism

    PubMed Central

    Lariguet, Patricia; Schepens, Isabelle; Hodgson, Daniel; Pedmale, Ullas V.; Trevisan, Martine; Kami, Chitose; de Carbonnel, Matthieu; Alonso, José M.; Ecker, Joseph R.; Liscum, Emmanuel; Fankhauser, Christian

    2006-01-01

    Phototropism, or plant growth in response to unidirectional light, is an adaptive response of crucial importance. Lateral differences in low fluence rates of blue light are detected by phototropin 1 (phot1) in Arabidopsis. Only NONPHOTOTROPIC HYPOCOTYL 3 (NPH3) and root phototropism 2, both belonging to the same family of proteins, have been previously identified as phototropin-interacting signal transducers involved in phototropism. PHYTOCHROME KINASE SUBSTRATE (PKS) 1 and PKS2 are two phytochrome signaling components belonging to a small gene family in Arabidopsis (PKS1–PKS4). The strong enhancement of PKS1 expression by blue light and its light induction in the elongation zone of the hypocotyl prompted us to study the function of this gene family during phototropism. Photobiological experiments show that the PKS proteins are critical for hypocotyl phototropism. Furthermore, PKS1 interacts with phot1 and NPH3 in vivo at the plasma membrane and in vitro, indicating that the PKS proteins may function directly with phot1 and NPH3 to mediate phototropism. The phytochromes are known to influence phototropism but the mechanism involved is still unclear. We show that PKS1 induction by a pulse of blue light is phytochrome A-dependent, suggesting that the PKS proteins may provide a molecular link between these two photoreceptor families. PMID:16777956

  12. Spatial separation of light perception and growth response in maize root phototropism.

    PubMed

    Mullen, J L; Wolverton, C; Ishikawa, H; Hangarter, R P; Evans, M L

    2002-09-01

    Although the effects of gravity on root growth are well known and interactions between light and gravity have been reported, details of root phototropic responses are less documented. We used high-resolution image analysis to study phototropism in primary roots of Zea mays L. Similar to the location of perception in gravitropism, the perception of light was localized in the root cap. Phototropic curvature away from the light, on the other hand, developed in the central elongation zone, more basal than the site of initiation of gravitropic curvature. The phototropic curvature saturated at approximately 10 micromoles m-2 s-1 blue light with a peak curvature of 29 +/- 4 degrees, in part due to induction of positive gravitropism following displacement of the root tip from vertical during negative phototropism. However, at higher fluence rates, development of phototropic curvature is arrested even if gravitropism is avoided by maintaining the root cap vertically using a rotating feedback system. Thus continuous illumination can cause adaptation in the signalling pathway of the phototropic response in roots.

  13. Spatial separation of light perception and growth response in maize root phototropism

    NASA Technical Reports Server (NTRS)

    Mullen, J. L.; Wolverton, C.; Ishikawa, H.; Hangarter, R. P.; Evans, M. L.

    2002-01-01

    Although the effects of gravity on root growth are well known and interactions between light and gravity have been reported, details of root phototropic responses are less documented. We used high-resolution image analysis to study phototropism in primary roots of Zea mays L. Similar to the location of perception in gravitropism, the perception of light was localized in the root cap. Phototropic curvature away from the light, on the other hand, developed in the central elongation zone, more basal than the site of initiation of gravitropic curvature. The phototropic curvature saturated at approximately 10 micromoles m-2 s-1 blue light with a peak curvature of 29 +/- 4 degrees, in part due to induction of positive gravitropism following displacement of the root tip from vertical during negative phototropism. However, at higher fluence rates, development of phototropic curvature is arrested even if gravitropism is avoided by maintaining the root cap vertically using a rotating feedback system. Thus continuous illumination can cause adaptation in the signalling pathway of the phototropic response in roots.

  14. Genetic separation of phototropism from blue light inhibition of hypocotyl elongation on Arabidopsis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liscum, E.; Young, J.C.; Hangarter, R.P.

    1991-05-01

    Phototropism and inhibition of stem elongation occur in response to blue light-induced inhibition of cell elongation. However, phototropism is a low fluence response and inhibition of hypocotyl elongation is a high irradiance response. The authors have isolated several mutant lines of Arabidopsis which lack blue light-induced inhibition of hypocotyl elongation but retain normal phototropic functions. In addition, a mutant line which completely lacks the phototropic response retains normal blue light-induced inhibition of hypocotyl elongation. F1 progeny of crosses between these two mutant classes exhibited wild-type phototropism and inhibition of hypocotyl elongation in response to blue light stimuli. In the F2more » generation, one in sixteen seedlings were double mutants lacking both phototropism and blue light-induced hypocotyl growth inhibition. These studies conclusively show that blue light-induced phototropism and hypocotyl growth inhibition function through genetically distinct signal transduction or response systems.« less

  15. The Rice COLEOPTILE PHOTOTROPISM1 Gene Encoding an Ortholog of Arabidopsis NPH3 Is Required for Phototropism of Coleoptiles and Lateral Translocation of AuxinW⃞

    PubMed Central

    Haga, Ken; Takano, Makoto; Neumann, Ralf; Iino, Moritoshi

    2005-01-01

    We isolated a mutant, named coleoptile phototropism1 (cpt1), from γ-ray–mutagenized japonica-type rice (Oryza sativa). This mutant showed no coleoptile phototropism and severely reduced root phototropism after continuous stimulation. A map-based cloning strategy and transgenic complementation test were applied to demonstrate that a NPH3-like gene deleted in the mutant corresponds to CPT1. Phylogenetic analysis of putative CPT1 homologs of rice and related proteins indicated that CPT1 has an orthologous relationship with Arabidopsis thaliana NPH3. These results, along with those for Arabidopsis, demonstrate that NPH3/CPT1 is a key signal transduction component of higher plant phototropism. In an extended study with the cpt1 mutant, it was found that phototropic differential growth is accompanied by a CPT1-independent inhibition of net growth. Kinetic investigation further indicated that a small phototropism occurs in cpt1 coleoptiles. This response, induced only transiently, was thought to be caused by the CPT1-independent growth inhibition. The 3H-indole-3-acetic acid applied to the coleoptile tip was asymmetrically distributed between the two sides of phototropically responding coleoptiles. However, no asymmetry was induced in cpt1 coleoptiles, indicating that lateral translocation of auxin occurs downstream of CPT1. It is concluded that the CPT1-dependent major phototropism of coleoptiles is achieved by lateral auxin translocation and subsequent growth redistribution. PMID:15598797

  16. Mutants of Arabidopsis thaliana with altered phototropism

    NASA Technical Reports Server (NTRS)

    Khurana, J. P.; Poff, K. L.

    1989-01-01

    Thirty five strains of Arabidopsis thaliana (L.) Heynh. have been identified with altered phototropic responses to 450-nm light. Four of these mutants have been more thoroughly characterized. Strain JK224 shows normal gravitropism and "second positive" phototropism. However, while the amplitude for "first positive" phototropism is the same as that in the wild-type, the threshold and fluence for the maximum response in "first positive" phototropism are shifted to higher fluence by a factor of 20-30. This mutant may represent an alteration in the photoreceptor pigment for phototropism. Strain JK218 exhibits no curvature to light at any fluence from 1 micromole m-2 to 2700 micromoles m-2, but shows normal gravitropism. Strain JK345 shows no "first positive" phototropism, and reduced gravitropism and "second positive" phototropism. Strain JK229 shows no measurable "first positive" phototropism, but normal gravitropism and "second positive" phototropism. Based on these data, it is suggested that: 1. gravitropism and phototropism contain at least one common element; 2. "first positive" and "second positive" phototropism contain at least one common element; and 3. "first positive" phototropism can be substantially altered without any apparent alteration of "second positive" phototropism.

  17. PIN Auxin Efflux Carriers Are Necessary for Pulse-Induced But Not Continuous Light-Induced Phototropism in Arabidopsis1[W][OA

    PubMed Central

    Haga, Ken; Sakai, Tatsuya

    2012-01-01

    Auxin efflux carrier PIN-FORMED (PIN) proteins are thought to have central roles in regulating asymmetrical auxin translocation during tropic responses, including gravitropism and phototropism, in plants. Although PIN3 is known to be involved in phototropism in Arabidopsis (Arabidopsis thaliana), no severe defects of phototropism in any of the pin mutants have been reported. We show here that the pulse-induced, first positive phototropism is impaired partially in pin1, pin3, and pin7 single mutants, and severely in triple mutants. In contrast, such impairment was not observed in continuous-light-induced second positive phototropism. Analysis with an auxin-reporter gene demonstrated that PIN3-mediated auxin gradients participate in pulse-induced phototropism but not in continuous-light-induced phototropism. Similar functional separation was also applicable to PINOID, a regulator of PIN localization. Our results strongly suggest the existence of functionally distinct mechanisms i.e. a PIN-dependent mechanism in which transient stimulation is sufficient to induce phototropism, and a PIN-independent mechanism that requires continuous stimulation and does not operate in the former phototropism process. Although a previous study has proposed that blue-light photoreceptors, the phototropins, control PIN localization through the transcriptional down-regulation of PINOID, we could not detect this blue-light-dependent down-regulation event, suggesting that other as yet unknown mechanisms are involved in phototropin-mediated phototropic responses. PMID:22843667

  18. Shoot phototropism in higher plants: new light through old concepts.

    PubMed

    Christie, John M; Murphy, Angus S

    2013-01-01

    Light is a key environmental factor that drives many aspects of plant growth and development. Phototropism, the reorientation of growth toward or away from light, represents one of these important adaptive processes. Modern studies of phototropism began with experiments conducted by Charles Darwin demonstrating that light perception at the shoot apex of grass coleoptiles induces differential elongation in the lower epidermal cells. This led to the discovery of the plant growth hormone auxin and the Cholodny-Went hypothesis attributing differential tropic bending to lateral auxin relocalization. In the past two decades, molecular-genetic analyses in the model flowering plant Arabidopsis thaliana has identified the principal photoreceptors for phototropism and their mechanism of activation. In addition, several protein families of auxin transporters have been identified. Despite extensive efforts, however, it still remains unclear as to how photoreceptor activation regulates lateral auxin transport to establish phototropic growth. This review aims to summarize major developments from over the last century and how these advances shape our current understanding of higher plant phototropism. Recent progress in phototropism research and the way in which this research is shedding new light on old concepts, including the Cholodny-Went hypothesis, is also highlighted.

  19. Arabidopsis G-protein β subunit AGB1 interacts with NPH3 and is involved in phototropism.

    PubMed

    Kansup, Jeeraporn; Tsugama, Daisuke; Liu, Shenkui; Takano, Tetsuo

    2014-02-28

    Heterotrimeric G proteins (Gα, Gβ and Gγ) have pleiotropic roles in plants, but molecular mechanisms underlying them remain to be elucidated. Here we show that Arabidopsis Gβ (AGB1) interacts with NPH3, a regulator of phototropism. Yeast two-hybrid assays, in vitro pull-down assays and bimolecular fluorescence complementation assays showed that AGB1 and NPH3 physically interact. NPH3-null mutation (nph3) is known to completely abolish hypocotyl phototropism. Loss-of-function mutants of AGB1 (agb1-1 and agb1-2) showed decreased hypocotyl phototropism, and agb1/nph3 double mutants showed no hypocotyl phototropism. These results suggest that AGB1 is involved in the NPH3-mediated regulation of phototropism. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism and other light responses.

    PubMed

    Idnurm, Alexander; Rodríguez-Romero, Julio; Corrochano, Luis M; Sanz, Catalina; Iturriaga, Enrique A; Eslava, Arturo P; Heitman, Joseph

    2006-03-21

    Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served as a model for the detection of environmental signals as diverse as light, chemicals, touch, wind, gravity, and adjacent objects. In particular, sporangiophore growth is regulated by light, and it exhibits phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses. The Phycomyces madA mutants were first isolated more than 40 years ago, and they exhibit reduced sensitivity to light. Here, we identify two (duplicated) homologs in the White Collar 1 family of blue-light photoreceptors in Phycomyces. We describe that the madA mutant strains contain point mutations in one of these genes and that these mutations cosegregate with a defect in phototropism after genetic crosses. Thus, the phototropic responses of fungi through madA and plants through phototropin rely on diverse proteins; however, these proteins share a conserved flavin-binding domain for photon detection.

  1. The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism and other light responses

    PubMed Central

    Idnurm, Alexander; Rodríguez-Romero, Julio; Corrochano, Luis M.; Sanz, Catalina; Iturriaga, Enrique A.; Eslava, Arturo P.; Heitman, Joseph

    2006-01-01

    Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served as a model for the detection of environmental signals as diverse as light, chemicals, touch, wind, gravity, and adjacent objects. In particular, sporangiophore growth is regulated by light, and it exhibits phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses. The Phycomyces madA mutants were first isolated more than 40 years ago, and they exhibit reduced sensitivity to light. Here, we identify two (duplicated) homologs in the White Collar 1 family of blue-light photoreceptors in Phycomyces. We describe that the madA mutant strains contain point mutations in one of these genes and that these mutations cosegregate with a defect in phototropism after genetic crosses. Thus, the phototropic responses of fungi through madA and plants through phototropin rely on diverse proteins; however, these proteins share a conserved flavin-binding domain for photon detection. PMID:16537433

  2. Phytochrome A Mediates Blue-Light Enhancement of Second-Positive Phototropism in Arabidopsis.

    PubMed

    Sullivan, Stuart; Hart, Jaynee E; Rasch, Patrick; Walker, Catriona H; Christie, John M

    2016-01-01

    Hypocotyl phototropism of etiolated Arabidopsis seedlings is primarily mediated by the blue-light receptor kinase phototropin 1 (phot1). Phot1-mediated curvature to continuous unilateral blue light irradiation (0.5 μmol m(-2) s(-1)) is enhanced by overhead pre-treatment with red light (20 μmol m(-2) s(-1) for 15 min) through the action of phytochrome (phyA). Here, we show that pre-treatment with blue light is equally as effective in eliciting phototropic enhancement and is dependent on phyA. Although blue light pre-treatment was sufficient to activate early phot1 signaling events, phot1 autophosphorylation in vivo was not found to be saturated, as assessed by subsequently measuring phot1 kinase activity in vitro. However, enhancement effects by red and blue light pre-treatment were not observed at higher intensities of phototropic stimulation (10 μmol m(-2) s(-1)). Phototropic enhancement by red and blue light pre-treatments to 0.5 μmol m(-2) s(-1) unilateral blue light irradiation was also lacking in transgenic Arabidopsis where PHOT1 expression was restricted to the epidermis. Together, these findings indicate that phyA-mediated effects on phot1 signaling are restricted to low intensities of phototropic stimulation and originate from tissues other than the epidermis.

  3. Physiological Analysis of Phototropic Responses in Arabidopsis.

    PubMed

    Zeidler, Mathias

    2016-01-01

    Plants utilize light as sole energy source. To maximize light capture they are able to detect the light direction and orient themselves towards the light source. This phototropic response is mediated by the plant blue light photoreceptors phototropin1 and 2 (phot1 and phot2). Although fully differentiated plants also exhibit this response it can be best observed in etiolated seedlings. Differences in light between the illuminated and shaded site of a seedling stem lead to changes in the auxin-distribution, resulting in cell elongation on the shaded site. Since phototropism connects light perception, signaling, and auxin transport, it is of great interest to analyze this response with a fast and simple method.Here we describe a method to analyze the phototropic response of Arabidopsis seedlings. With numerous mutants available, its fast germination and its small size Arabidopsis is well suited for this analysis. Different genotypes can be simultaneously probed in less than a week.

  4. Phytochrome A Mediates Blue-Light Enhancement of Second-Positive Phototropism in Arabidopsis

    PubMed Central

    Sullivan, Stuart; Hart, Jaynee E.; Rasch, Patrick; Walker, Catriona H.; Christie, John M.

    2016-01-01

    Hypocotyl phototropism of etiolated Arabidopsis seedlings is primarily mediated by the blue-light receptor kinase phototropin 1 (phot1). Phot1-mediated curvature to continuous unilateral blue light irradiation (0.5 μmol m−2 s−1) is enhanced by overhead pre-treatment with red light (20 μmol m−2 s−1 for 15 min) through the action of phytochrome (phyA). Here, we show that pre-treatment with blue light is equally as effective in eliciting phototropic enhancement and is dependent on phyA. Although blue light pre-treatment was sufficient to activate early phot1 signaling events, phot1 autophosphorylation in vivo was not found to be saturated, as assessed by subsequently measuring phot1 kinase activity in vitro. However, enhancement effects by red and blue light pre-treatment were not observed at higher intensities of phototropic stimulation (10 μmol m−2 s−1). Phototropic enhancement by red and blue light pre-treatments to 0.5 μmol m−2 s−1 unilateral blue light irradiation was also lacking in transgenic Arabidopsis where PHOT1 expression was restricted to the epidermis. Together, these findings indicate that phyA-mediated effects on phot1 signaling are restricted to low intensities of phototropic stimulation and originate from tissues other than the epidermis. PMID:27014313

  5. Phototropism: a "simple" physiological response modulated by multiple interacting photosensory-response pathways.

    PubMed

    Liscum, E; Stowe-Evans, E L

    2000-09-01

    Phototropism is the process by which plants reorient growth of various organs, most notably stems, in response to lateral differences in light quantity and/or quality. The ubiquitous nature of the phototropic response in the plant kingdom implies that it provides some adaptive evolutionary advantage. Upon visual inspection it is tempting to surmise that phototropic curvatures result from a relatively simple growth response to a directional stimulus. However, detailed photophysiological, and more recently genetic and molecular, studies have demonstrated that phototropism is in fact regulated by complex interactions among several photosensory systems. At least two receptors, phototropin and a presently unidentified receptor, appear to mediate the primary photoreception of directional blue light cues in dark-grown plants. PhyB may also function as a primary receptor to detect lateral increases in far-red light in neighbor-avoidance responses of light-grown plants. Phytochromes (phyA and phyB at a minimum) also appear to function as secondary receptors to regulate adaptation processes that ultimately modulate the magnitude of curvature induced by primary photoperception. As a result of the interactions of these multiple photosensory systems plants are able to maximize the adaptive advantage of the phototropic response in ever changing light environments.

  6. Phototropism: mechanism and outcomes.

    PubMed

    Pedmale, Ullas V; Celaya, R Brandon; Liscum, Emmanuel

    2010-01-01

    Plants have evolved a wide variety of responses that allow them to adapt to the variable environmental conditions in which they find themselves growing. One such response is the phototropic response - the bending of a plant organ toward (stems and leaves) or away from (roots) a directional blue light source. Phototropism is one of several photoresponses of plants that afford mechanisms to alter their growth and development to changes in light intensity, quality and direction. Over recent decades much has been learned about the genetic, molecular and cell biological components involved in sensing and responding to phototropic stimuli. Many of these advances have been made through the utilization of Arabidopsis as a model for phototropic studies. Here we discuss such advances, as well as studies in other plant species where appropriate to the discussion of work in Arabidopsis.

  7. Disruptions in AUX1-dependent auxin influx alter hypocotyl phototropism in Arabidopsis.

    PubMed

    Stone, Bethany B; Stowe-Evans, Emily L; Harper, Reneé M; Celaya, R Brandon; Ljung, Karin; Sandberg, Göran; Liscum, Emmanuel

    2008-01-01

    Phototropism represents a differential growth response by which plant organs can respond adaptively to changes in the direction of incident light to optimize leaf/stem positioning for photosynthetic light capture and root growth orientation for water/nutrient acquisition. Studies over the past few years have identified a number of components in the signaling pathway(s) leading to development of phototropic curvatures in hypocotyls. These include the phototropin photoreceptors (phot1 and phot2) that perceive directional blue-light (BL) cues and then stimulate signaling, leading to relocalization of the plant hormone auxin, as well as the auxin response factor NPH4/ARF7 that responds to changes in local auxin concentrations to directly mediate expression of genes likely encoding proteins necessary for development of phototropic curvatures. While null mutations in NPH4/ARF7 condition an aphototropic response to unidirectional BL, seedlings carrying the same mutations recover BL-dependent phototropic responsiveness if co-irradiated with red light (RL) or pre-treated with either ethylene. In the present study, we identify second-site enhancer mutations in the nph4 background that abrogate these recovery responses. One of these mutations--map1 (modifier of arf7 phenotypes 1)--was found to represent a missense allele of AUX1--a gene encoding a high-affinity auxin influx carrier previously associated with a number of root responses. Pharmacological studies and analyses of additional aux1 mutants confirmed that AUX1 functions as a modulator of hypocotyl phototropism. Moreover, we have found that the strength of dependence of hypocotyl phototropism on AUX1-mediated auxin influx is directly related to the auxin responsiveness of the seedling in question.

  8. Phototropins Function in High-Intensity Blue Light-Induced Hypocotyl Phototropism in Arabidopsis by Altering Cytosolic Calcium1[C][W][OA

    PubMed Central

    Zhao, Xiang; Wang, Yan-Liang; Qiao, Xin-Rong; Wang, Jin; Wang, Lin-Dan; Xu, Chang-Shui; Zhang, Xiao

    2013-01-01

    Phototropins (phot1 and phot2), the blue light receptors in plants, regulate hypocotyl phototropism in a fluence-dependent manner. Especially under high fluence rates of blue light (HBL), the redundant function mediated by both phot1 and phot2 drastically restricts the understanding of the roles of phot2. Here, systematic analysis of phototropin-related mutants and overexpression transgenic lines revealed that HBL specifically induced a transient increase in cytosolic Ca2+ concentration ([Ca2+]cyt) in Arabidopsis (Arabidopsis thaliana) hypocotyls and that the increase in [Ca2+]cyt was primarily attributed to phot2. Pharmacological and genetic experiments illustrated that HBL-induced Ca2+ increases were modulated differently by phot1 and phot2. Phot2 mediated the HBL-induced increase in [Ca2+]cyt mainly by an inner store-dependent Ca2+-release pathway, not by activating plasma membrane Ca2+ channels. Further analysis showed that the increase in [Ca2+]cyt was possibly responsible for HBL-induced hypocotyl phototropism. An inhibitor of auxin efflux carrier exhibited significant inhibitions of both phototropism and increases in [Ca2+]cyt, which indicates that polar auxin transport is possibly involved in HBL-induced responses. Moreover, PHYTOCHROME KINASE SUBSTRATE1 (PKS1), the phototropin-related signaling element identified, interacted physically with phototropins, auxin efflux carrier PIN-FORMED1 and calcium-binding protein CALMODULIN4, in vitro and in vivo, respectively, and HBL-induced phototropism was impaired in pks multiple mutants, indicating the role of the PKS family in HBL-induced phototropism. Together, these results provide new insights into the functions of phototropins and highlight a potential integration point through which Ca2+ signaling-related HBL modulates hypocotyl phototropic responses. PMID:23674105

  9. D6PK AGCVIII Kinases Are Required for Auxin Transport and Phototropic Hypocotyl Bending in Arabidopsis[C][W

    PubMed Central

    Willige, Björn C.; Ahlers, Siv; Zourelidou, Melina; Barbosa, Inês C.R.; Demarsy, Emilie; Trevisan, Martine; Davis, Philip A.; Roelfsema, M. Rob G.; Hangarter, Roger; Fankhauser, Christian; Schwechheimer, Claus

    2013-01-01

    Phototropic hypocotyl bending in response to blue light excitation is an important adaptive process that helps plants to optimize their exposure to light. In Arabidopsis thaliana, phototropic hypocotyl bending is initiated by the blue light receptors and protein kinases phototropin1 (phot1) and phot2. Phototropic responses also require auxin transport and were shown to be partially compromised in mutants of the PIN-FORMED (PIN) auxin efflux facilitators. We previously described the D6 PROTEIN KINASE (D6PK) subfamily of AGCVIII kinases, which we proposed to directly regulate PIN-mediated auxin transport. Here, we show that phototropic hypocotyl bending is strongly dependent on the activity of D6PKs and the PIN proteins PIN3, PIN4, and PIN7. While early blue light and phot-dependent signaling events are not affected by the loss of D6PKs, we detect a gradual loss of PIN3 phosphorylation in d6pk mutants of increasing complexity that is most severe in the d6pk d6pkl1 d6pkl2 d6pkl3 quadruple mutant. This is accompanied by a reduction of basipetal auxin transport in the hypocotyls of d6pk as well as in pin mutants. Based on our data, we propose that D6PK-dependent PIN regulation promotes auxin transport and that auxin transport in the hypocotyl is a prerequisite for phot1-dependent hypocotyl bending. PMID:23709629

  10. Blue-light-induced PIN3 polarization for root negative phototropic response in Arabidopsis.

    PubMed

    Zhang, Kun-Xiao; Xu, Heng-Hao; Yuan, Ting-Ting; Zhang, Liang; Lu, Ying-Tang

    2013-10-01

    Root negative phototropism is an important response in plants. Although blue light is known to mediate this response, the cellular and molecular mechanisms underlying root negative phototropism remain unclear. Here, we report that the auxin efflux carrier PIN-FORMED (PIN) 3 is involved in asymmetric auxin distribution and root negative phototropism. Unilateral blue-light illumination polarized PIN3 to the outer lateral membrane of columella cells at the illuminated root side, and increased auxin activity at the illuminated side of roots, where auxin promotes growth and causes roots bending away from the light source. Furthermore, root negative phototropic response and blue-light-induced PIN3 polarization were modulated by a brefeldin A-sensitive, GNOM-dependent, trafficking pathway and by phot1-regulated PINOID (PID)/PROTEIN PHOSPHATASE 2A (PP2A) activity. Our results indicate that blue-light-induced PIN3 polarization is needed for asymmetric auxin distribution during root negative phototropic response. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  11. Root phototropism: from dogma to the mechanism of blue light perception.

    PubMed

    Kutschera, Ulrich; Briggs, Winslow R

    2012-03-01

    In roots, the "hidden half" of all land plants, gravity is an important signal that determines the direction of growth in the soil. Hence, positive gravitropism has been studied in detail. However, since the 19th century, the response of roots toward unilateral light has also been analyzed. Based on studies on white mustard (Sinapis alba) seedlings, botanists have concluded that all roots are negatively phototropic. This "Sinapis-dogma" was refuted in a seminal study on root phototropism published a century ago, where it was shown that less then half of the 166 plant species investigated behave like S. alba, whereas 53% displayed no phototropic response at all. Here we summarize the history of research on root phototropism, discuss this phenomenon with reference to unpublished data on garden cress (Lepidium sativum) seedlings, and describe the effects of blue light on the negative bending response in Thale cress (Arabidopsis thaliana). The ecological significance of root phototropism is discussed and the relationships between gravi- and phototropism are outlined, with respect to the starch-statolith-theory of gravity perception. Finally, we present an integrative model of gravi- and blue light perception in the root tip of Arabidopsis seedlings. This hypothesis is based on our current view of the starch-statolith-concept and light sensing via the cytoplasmic red/blue light photoreceptor phytochrome A and the plasma membrane-associated blue light receptor phototropin-1. Open questions and possible research agendas for the future are summarized.

  12. The signal transducer NPH3 integrates the phototropin1 photosensor with PIN2-based polar auxin transport in Arabidopsis root phototropism.

    PubMed

    Wan, Yinglang; Jasik, Jan; Wang, Li; Hao, Huaiqing; Volkmann, Dieter; Menzel, Diedrik; Mancuso, Stefano; Baluška, František; Lin, Jinxing

    2012-02-01

    Under blue light (BL) illumination, Arabidopsis thaliana roots grow away from the light source, showing a negative phototropic response. However, the mechanism of root phototropism is still unclear. Using a noninvasive microelectrode system, we showed that the BL sensor phototropin1 (phot1), the signal transducer NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and the auxin efflux transporter PIN2 were essential for BL-induced auxin flux in the root apex transition zone. We also found that PIN2-green fluorescent protein (GFP) localized to vacuole-like compartments (VLCs) in dark-grown root epidermal and cortical cells, and phot1/NPH3 mediated a BL-initiated pathway that caused PIN2 redistribution to the plasma membrane. When dark-grown roots were exposed to brefeldin A (BFA), PIN2-GFP remained in VLCs in darkness, and BL caused PIN2-GFP disappearance from VLCs and induced PIN2-GFP-FM4-64 colocalization within enlarged compartments. In the nph3 mutant, both dark and BL BFA treatments caused the disappearance of PIN2-GFP from VLCs. However, in the phot1 mutant, PIN2-GFP remained within VLCs under both dark and BL BFA treatments, suggesting that phot1 and NPH3 play different roles in PIN2 localization. In conclusion, BL-induced root phototropism is based on the phot1/NPH3 signaling pathway, which stimulates the shootward auxin flux by modifying the subcellular targeting of PIN2 in the root apex transition zone.

  13. PKS1 plays a role in red-light-based positive phototropism in roots.

    PubMed

    Molas, Maria Lia; Kiss, John Z

    2008-06-01

    Aerial parts of plants curve towards the light (i.e. positive phototropism), and roots typically grow away from the light (i.e. negative phototropism). In addition, Arabidopsis roots exhibit positive phototropism relative to red light (RL), and this response is mediated by phytochromes A and B (phyA and phyB). Upon light stimulation, phyA and phyB interact with the phytochrome kinase substrate (PKS1) in the cytoplasm. In this study, we investigated the role of PKS1, along with phyA and phyB, in the positive phototropic responses to RL in roots. Using a high-resolution feedback system, we studied the phenotypic responses of roots of phyA, phyB, pks1, phyA pks1 and phyB pks1 null mutants as well as the PKS1-overexpressing line in response to RL. PKS1 emerged as an intermediary in the signalling pathways and appears to promote a negative curvature to RL in roots. In addition, phyA and phyB were both essential for a positive response to RL and act in a complementary fashion. However, either photoreceptor acting without the other results in negative curvature in response to red illumination so that the mode of action differs depending on whether phyA and phyB act independently or together. Our results suggest that PKS1 is part of a signalling pathway independent of phyA and phyB and that PKS1 modulates RL-based root phototropism.

  14. Red-light-induced positive phototropism in Arabidopsis roots

    NASA Technical Reports Server (NTRS)

    Ruppel, N. J.; Hangarter, R. P.; Kiss, J. Z.

    2001-01-01

    The interaction between light and gravity is critical in determining the final form of a plant. For example, the competing activities of gravitropism and phototropism can determine the final orientation of a stem or root. The results reported here indicate that, in addition to the previously described blue-light-dependent negative phototropic response in roots, roots of Arahidopsis thaliana (L.) Heynh. display a previously unknown red-light-dependent positive phototropic response. Both phototropic responses in roots are considerably weaker than the graviresponse, which often masks phototropic curvature. However, through the use of mutant strains with impaired gravitropism, we were able to identify a red-light-dependent positive phototropic response in Arabidopsis roots. The red-induced positive phototropic response is considerably weaker than the blue-light response and is barely detectable in plants with a normal gravitropic response.

  15. Red-light-induced positive phototropism in Arabidopsis roots.

    PubMed

    Ruppel, N J; Hangarter, R P; Kiss, J Z

    2001-02-01

    The interaction between light and gravity is critical in determining the final form of a plant. For example, the competing activities of gravitropism and phototropism can determine the final orientation of a stem or root. The results reported here indicate that, in addition to the previously described blue-light-dependent negative phototropic response in roots, roots of Arahidopsis thaliana (L.) Heynh. display a previously unknown red-light-dependent positive phototropic response. Both phototropic responses in roots are considerably weaker than the graviresponse, which often masks phototropic curvature. However, through the use of mutant strains with impaired gravitropism, we were able to identify a red-light-dependent positive phototropic response in Arabidopsis roots. The red-induced positive phototropic response is considerably weaker than the blue-light response and is barely detectable in plants with a normal gravitropic response.

  16. The Signal Transducer NPH3 Integrates the Phototropin1 Photosensor with PIN2-Based Polar Auxin Transport in Arabidopsis Root Phototropism[C][W

    PubMed Central

    Wan, Yinglang; Jasik, Jan; Wang, Li; Hao, Huaiqing; Volkmann, Dieter; Menzel, Diedrik; Mancuso, Stefano; Baluška, František; Lin, Jinxing

    2012-01-01

    Under blue light (BL) illumination, Arabidopsis thaliana roots grow away from the light source, showing a negative phototropic response. However, the mechanism of root phototropism is still unclear. Using a noninvasive microelectrode system, we showed that the BL sensor phototropin1 (phot1), the signal transducer NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and the auxin efflux transporter PIN2 were essential for BL-induced auxin flux in the root apex transition zone. We also found that PIN2-green fluorescent protein (GFP) localized to vacuole-like compartments (VLCs) in dark-grown root epidermal and cortical cells, and phot1/NPH3 mediated a BL-initiated pathway that caused PIN2 redistribution to the plasma membrane. When dark-grown roots were exposed to brefeldin A (BFA), PIN2-GFP remained in VLCs in darkness, and BL caused PIN2-GFP disappearance from VLCs and induced PIN2-GFP-FM4-64 colocalization within enlarged compartments. In the nph3 mutant, both dark and BL BFA treatments caused the disappearance of PIN2-GFP from VLCs. However, in the phot1 mutant, PIN2-GFP remained within VLCs under both dark and BL BFA treatments, suggesting that phot1 and NPH3 play different roles in PIN2 localization. In conclusion, BL-induced root phototropism is based on the phot1/NPH3 signaling pathway, which stimulates the shootward auxin flux by modifying the subcellular targeting of PIN2 in the root apex transition zone. PMID:22374399

  17. Hypocotyl growth orientation in blue light is determined by phytochrome A inhibition of gravitropism and phototropin promotion of phototropism.

    PubMed

    Lariguet, Patricia; Fankhauser, Christian

    2004-12-01

    How developing seedlings integrate gravitropic and phototropic stimuli to determine their direction of growth is poorly understood. In this study we tested whether blue light influences hypocotyl gravitropism in Arabidopsis. Phototropin1 (phot1) triggers phototropism under low fluence rates of blue light but, at least in the dark, has no effect on gravitropism. By analyzing the growth orientation of phototropism-deficient seedlings in response to gravitropic and phototropic stimulations we show that blue light not only triggers phototropism but also represses hypocotyl gravitropism. At low fluence rates of blue light phot1 mutants were agravitropic. In contrast, phyAphot1 double mutants grew exclusively according to gravity demonstrating that phytochrome A (phyA) is necessary to inhibit gravitropism. Analyses of phot1cry1cry2 triple mutants indicate that cryptochromes play a minor role in this response. Thus the optimal growth orientation of hypocotyls is determined by the action of phyA-suppressing gravitropism and the phototropin-triggering phototropism. It has long been known that phytochromes promote phototropism but the mechanism involved is still unknown. Our data show that by inhibiting gravitropism phyA acts as a positive regulator of phototropism.

  18. Shade Promotes Phototropism through Phytochrome B-Controlled Auxin Production.

    PubMed

    Goyal, Anupama; Karayekov, Elizabeth; Galvão, Vinicius Costa; Ren, Hong; Casal, Jorge J; Fankhauser, Christian

    2016-12-19

    Phototropism is an asymmetric growth response enabling plants to optimally position their organs. In flowering plants, the phototropin (phot) blue light receptors are essential to detect light gradients. In etiolated seedlings, the phototropic response is enhanced by the red/far-red (R/FR)-sensing phytochromes (phy) with a predominant function of phyA. In this study, we analyzed the influence of the phytochromes on phototropism in green (de-etiolated) Arabidopsis seedlings. Our experiments in the laboratory and outdoors revealed that, in open environments (high R/FR ratio), phyB inhibits phototropism. In contrast, under foliar shade, where access to direct sunlight becomes important, the phototropic response was strong. phyB modulates phototropism, depending on the R/FR ratio, by controlling the activity of three basic-helix-loop-helix (bHLH) transcription factors of the PHYTOCHROME INTERACTING FACTORs (PIFs) family. Promotion of phototropism depends on PIF-mediated induction of several members of the YUCCA gene family, leading to auxin production in the cotyledons. Our study identifies PIFs and YUCCAs as novel molecular players promoting phototropism in photoautotrophic, but not etiolated, seedlings. Moreover, our findings reveal fundamental differences in the phytochrome-phototropism crosstalk in etiolated versus green seedlings. We propose that in natural conditions where the light environment is not homogeneous, the uncovered phytochrome-phototropin co-action is important for plants to adapt their growth strategy to optimize photosynthetic light capture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Phototropism in Arabidopsis roots is mediated by two sensory systems

    NASA Astrophysics Data System (ADS)

    Kiss, John Z.; Ruppel, Nicholas J.; Hangarter, Roger P.

    Phototropism has been well-characterized in stems and stem-like organs, but there have been relatively few studies of root phototropism. Our experiments suggest that there are two photosensory systems that elicit phototropic responses in roots of Arabidopsis thaliana: a previously identified blue-light photoreceptor system mediated by phototropin (= NPH1 protein) and a novel red-light-based mechanism. The phototropic responses in roots are much weaker than the graviresponse, which competes with and often masks the phototropic response. It was through the use of mutant plants with a weakened graviresponse that we were able to identify the activity of the red-light-dependent phototropic system. In addition, the red-light-based photoresponse in roots is even weaker compared to the blue-light response. Our results also suggest that phytochrome may be involved in mediating positive phototropism in roots.

  20. Novel hydrotropism mutants of Arabidopsis thaliana and their altered waving response and phototropism.

    PubMed

    Takahashi, Akiko; Kobayashi, Akie; Kakimoto, Yoko; Fujii, Nobuharu; Takahashi, Hideyuki

    2003-10-01

    Roots display positive hydrotropism in response to a moisture gradient, which is important for plants to escape from water stress and regulate the directional growth by interacting with other growth movements such as gravitropism, phototropism and waving response. On Earth, hydrotropism is interfered by gravitropism in particular, so that microgravity conditions or agravitropic mutants have been used for the study of hydrotropism. However, we have recently established an experimental system for the study of hydrotropism in Arabidopsis roots that easily develop hydrotropism in response to moisture gradient by overcoming gravitropism. Using the Arabidopsis system, we isolated hydrotropism mutants named root hydrotropism (rhy). In the present study, we examined the hydrotropism, gravitropism, phototropism, waving response and elongation growth of rhy4 and rhy5 roots that were defective in positive hydrotropism. Interestingly, rhy4 roots curved away from the water source and showed a reduced waving response. Both rhy4 and rhy5 showed normal gravitropism and a slight reduction in phototropism. These results suggest that there is a mutual molecular mechanism underlying hydrotropism, waving response and/or phototropism. Thus, we have obtained novel hydrotropic mutants that will be used for revealing molecular mechanism of root hydrotropism and its interaction with waving response and/or phototropism.

  1. KINETIC STUDIES OF PHOTOTROPIC REACTIONS OF TRIPHENYLMETHANE LEUCONITRILES

    DTIC Science & Technology

    The mechanism of the phototropic reaction of triphenylmethane leuconitriles was studied in considerable detail. For the reaction between methyl...violet and cyande is phototropic and on excitation with ultraviolet light will revert to the dye and cyanide. The role of the solvent in the... phototropic process is considered. The excitation energy of the photoropic process is estabished. (Author)

  2. OPERATIONAL TEST AND EVALUATION OF PHOTOTROPIC GOGGLES.

    DTIC Science & Technology

    Irreversible Phototropic Filter Device is one of many such systems. Forty-nine Air Defense Command and twenty-four Tactical Air Command aircrews evaluated the...indicated that: The goggles do not integrate with the oxygen mask, helmet and visor; It is not practicable to carry additional phototropic lenses for...in-flight changes. The Irreversible Phototropic Filter Device is operationally unacceptable for use by aircrew members. Recommend that ASD continue efforts to develop a suitable device for flashblindness protection. (Author)

  3. Phototropism in Arabidopsis roots is mediated by two sensory systems.

    PubMed

    Kiss, J Z; Ruppel, N J; Hangarter, R P

    2001-01-01

    Phototropism has been well-characterized in stems and stem-like organs, but there have been relatively few studies of root phototropism. Our experiments suggest that there are two photosensory systems that elicit phototropic responses in roots of Arabidopsis thaliana: a previously identified blue-light photoreceptor system mediated by phototropin (=NPH1 protein) and a novel red-light-based mechanism. The phototropic responses in roots are much weaker than the graviresponse, which competes with and often masks the phototropic response. It was through the use of mutant plants with a weakened graviresponse that we were able to identify the activity of the red-light-dependent phototropic system. In addition, the red-light-based photoresponse in roots is even weaker compared to the blue-light response. Our results also suggest that phytochrome may be involved in mediating positive phototropism in roots. c 2001 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  4. Growth distribution during phototropism of Arabidopsis thaliana seedlings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Orbovic, V.; Poff, K.L.

    1993-09-01

    The elongation rates of two opposite sides of hypocotyls of Arabidopsis thaliana seedlings were measured during phototropism by using an infrared imaging system. In first positive phototropism, second positive phototropism, and red light-enhanced first positive phototropism, curvature toward the light source was the result of an increase in the rate of elongation of the shaded side and a decrease in the rate of elongation of the lighted side of the seedlings. The phase of straightening that followed maximum curvature resulted from a decrease in the elongation rate of the shaded side and an increase in the elongation rate of themore » lighted side. These data for the three types of blue light-induced phototropism tested in this study and for the phase of straightening are all clearly consistent with the growth rate changes predicted by the Cholodny-Went theory. 31 refs., 7 figs.« less

  5. PHOTOTROPISM OF GERMINATING MYCELIA OF SOME PARASITIC FUNGI

    DTIC Science & Technology

    uredinales on young wheat plants; Distribution and significance of the phototropism of germinating mycelia -- confirmation of older data, examination of...eight additional uredinales, probable meaning of negative phototropism for the occurrence of infection; Analysis of the stimulus physiology of the...reaction -- the minimum effective illumination intensity, the effective special region, inversion of the phototropic reaction in liquid paraffin, the negative light- growth reaction, the light-sensitive zone.

  6. Phototropism and gravitropism in lateral roots of Arabidopsis

    NASA Technical Reports Server (NTRS)

    Kiss, John Z.; Miller, Kelley M.; Ogden, Lisa A.; Roth, Kelly K.

    2002-01-01

    Gravitropism and, to a lesser extent, phototropism have been characterized in primary roots, but little is known about structural/functional aspects of these tropisms in lateral roots. Therefore, in this study, we report on tropistic responses in lateral roots of Arabidopsis thaliana. Lateral roots initially are plagiogravitropic, but when they reach a length of approximately 10 mm, these roots grow downward and exhibit positive orthogravitropism. Light and electron microscopic studies demonstrate a correlation between positive gravitropism and development of columella cells with large, sedimented amyloplasts in wild-type plants. Lateral roots display negative phototropism in response to white and blue light and positive phototropism in response to red light. As is the case with primary roots, the photoresponse is weak relative to the graviresponse, but phototropism is readily apparent in starchless mutant plants, which are impaired in gravitropism. To our knowledge, this is the first report of phototropism of lateral roots in any plant species.

  7. Phototropism and gravitropism in lateral roots of Arabidopsis.

    PubMed

    Kiss, John Z; Miller, Kelley M; Ogden, Lisa A; Roth, Kelly K

    2002-01-01

    Gravitropism and, to a lesser extent, phototropism have been characterized in primary roots, but little is known about structural/functional aspects of these tropisms in lateral roots. Therefore, in this study, we report on tropistic responses in lateral roots of Arabidopsis thaliana. Lateral roots initially are plagiogravitropic, but when they reach a length of approximately 10 mm, these roots grow downward and exhibit positive orthogravitropism. Light and electron microscopic studies demonstrate a correlation between positive gravitropism and development of columella cells with large, sedimented amyloplasts in wild-type plants. Lateral roots display negative phototropism in response to white and blue light and positive phototropism in response to red light. As is the case with primary roots, the photoresponse is weak relative to the graviresponse, but phototropism is readily apparent in starchless mutant plants, which are impaired in gravitropism. To our knowledge, this is the first report of phototropism of lateral roots in any plant species.

  8. Light-dependent gravitropism and negative phototropism of inflorescence stems in a dominant Aux/IAA mutant of Arabidopsis thaliana, axr2.

    PubMed

    Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T

    2014-09-01

    Gravitropism and phototropism of the primary inflorescence stems were examined in a dominant Aux/IAA mutant of Arabidopsis, axr2/iaa7, which did not display either tropism in hypocotyls. axr2-1 stems completely lacked gravitropism in the dark but slowly regained it in light condition. Though wild-type stems showed positive phototropism, axr2 stems displayed negative phototropism with essentially the same light fluence-response curve as the wild type (WT). Application of 1-naphthaleneacetic acid-containing lanolin to the stem tips enhanced the positive phototropism of WT, and reduced the negative phototropism of axr2. Decapitation of stems caused a small negative phototropism in WT, but did not affect the negative phototropism of axr2. p-glycoprotein 1 (pgp1) pgp19 double mutants showed no phototropism, while decapitated double mutants exhibited negative phototropism. Expression of auxin-responsive IAA14/SLR, IAA19/MSG2 and SAUR50 genes was reduced in axr2 and pgp1 pgp19 stems relative to that of WT. These suggest that the phototropic response of stem is proportional to the auxin supply from the shoot apex, and that negative phototropism may be a basal response to unilateral blue-light irradiation when the levels of auxin or auxin signaling are reduced to the minimal level in the primary stems. In contrast, all of these treatments reduced or did not affect gravitropism in wild-type or axr2 stems. Tropic responses of the transgenic lines that expressed axr2-1 protein by the endodermis-specific promoter suggest that AXR2-dependent auxin response in the endodermis plays a more crucial role in gravitropism than in phototropism in stems but no significant roles in either tropism in hypocotyls.

  9. Arabidopsis nph1 and npl1: blue light receptors that mediate both phototropism and chloroplast relocation.

    PubMed

    Sakai, T; Kagawa, T; Kasahara, M; Swartz, T E; Christie, J M; Briggs, W R; Wada, M; Okada, K

    2001-06-05

    UV-A/blue light acts to regulate a number of physiological processes in higher plants. These include light-driven chloroplast movement and phototropism. The NPH1 gene of Arabidopsis encodes an autophosphorylating protein kinase that functions as a photoreceptor for phototropism in response to low-intensity blue light. However, nph1 mutants have been reported to exhibit normal phototropic curvature under high-intensity blue light, indicating the presence of an additional phototropic receptor. A likely candidate is the nph1 homologue, npl1, which has recently been shown to mediate the avoidance response of chloroplasts to high-intensity blue light in Arabidopsis. Here we demonstrate that npl1, like nph1, noncovalently binds the chromophore flavin mononucleotide (FMN) within two specialized PAS domains, termed LOV domains. Furthermore, when expressed in insect cells, npl1, like nph1, undergoes light-dependent autophosphorylation, indicating that npl1 also functions as a light receptor kinase. Consistent with this conclusion, we show that a nph1 npl1 double mutant exhibits an impaired phototropic response under both low- and high-intensity blue light. Hence, npl1 functions as a second phototropic receptor under high fluence rate conditions and is, in part, functionally redundant to nph1. We also demonstrate that both chloroplast accumulation in response to low-intensity light and chloroplast avoidance movement in response to high-intensity light are lacking in the nph1 npl1 double mutant. Our findings therefore indicate that nph1 and npl1 show partially overlapping functions in two different responses, phototropism and chloroplast relocation, in a fluence rate-dependent manner.

  10. Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism.

    PubMed

    Sanz, Catalina; Rodríguez-Romero, Julio; Idnurm, Alexander; Christie, John M; Heitman, Joseph; Corrochano, Luis M; Eslava, Arturo P

    2009-04-28

    The fungus Phycomyces blakesleeanus reacts to environmental signals, including light, gravity, touch, and the presence of nearby objects, by changing the speed and direction of growth of its fruiting body (sporangiophore). Phototropism, growth toward light, shares many features in fungi and plants but the molecular mechanisms remain to be fully elucidated. Phycomyces mutants with altered phototropism were isolated approximately 40 years ago and found to have mutations in the mad genes. All of the responses to light in Phycomyces require the products of the madA and madB genes. We showed that madA encodes a protein similar to the Neurospora blue-light photoreceptor, zinc-finger protein WC-1. We show here that madB encodes a protein similar to the Neurospora zinc-finger protein WC-2. MADA and MADB interact to form a complex in yeast 2-hybrid assays and when coexpressed in E. coli, providing evidence that phototropism and other responses to light are mediated by a photoresponsive transcription factor complex. The Phycomyces genome contains 3 genes similar to wc-1, and 4 genes similar to wc-2, many of which are regulated by light in a madA or madB dependent manner. We did not detect any interactions between additional WC proteins in yeast 2-hybrid assays, which suggest that MADA and MADB form the major photoreceptor complex in Phycomyces. However, the presence of multiple wc genes in Phycomyces may enable perception across a broad range of light intensities, and may provide specialized photoreceptors for distinct photoresponses.

  11. Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism

    PubMed Central

    Sanz, Catalina; Rodríguez-Romero, Julio; Idnurm, Alexander; Christie, John M.; Heitman, Joseph; Corrochano, Luis M.; Eslava, Arturo P.

    2009-01-01

    The fungus Phycomyces blakesleeanus reacts to environmental signals, including light, gravity, touch, and the presence of nearby objects, by changing the speed and direction of growth of its fruiting body (sporangiophore). Phototropism, growth toward light, shares many features in fungi and plants but the molecular mechanisms remain to be fully elucidated. Phycomyces mutants with altered phototropism were isolated ≈40 years ago and found to have mutations in the mad genes. All of the responses to light in Phycomyces require the products of the madA and madB genes. We showed that madA encodes a protein similar to the Neurospora blue-light photoreceptor, zinc-finger protein WC-1. We show here that madB encodes a protein similar to the Neurospora zinc-finger protein WC-2. MADA and MADB interact to form a complex in yeast 2-hybrid assays and when coexpressed in E. coli, providing evidence that phototropism and other responses to light are mediated by a photoresponsive transcription factor complex. The Phycomyces genome contains 3 genes similar to wc-1, and 4 genes similar to wc-2, many of which are regulated by light in a madA or madB dependent manner. We did not detect any interactions between additional WC proteins in yeast 2-hybrid assays, which suggest that MADA and MADB form the major photoreceptor complex in Phycomyces. However, the presence of multiple wc genes in Phycomyces may enable perception across a broad range of light intensities, and may provide specialized photoreceptors for distinct photoresponses. PMID:19380729

  12. Phototropism: translating light into directional growth.

    PubMed

    Hohm, Tim; Preuten, Tobias; Fankhauser, Christian

    2013-01-01

    Phototropism allows plants to align their photosynthetic tissues with incoming light. The direction of incident light is sensed by the phototropin family of blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light-activated protein kinases. The kinase activity of phototropins and phosphorylation of residues in the activation loop of their kinase domains are essential for the phototropic response. These initial steps trigger the formation of the auxin gradient across the hypocotyl that leads to asymmetric growth. The molecular events between photoreceptor activation and the growth response are only starting to be elucidated. In this review, we discuss the major steps leading from light perception to directional growth concentrating on Arabidopsis. In addition, we highlight links that connect these different steps enabling the phototropic response.

  13. Arabidopsis nph1 and npl1: Blue light receptors that mediate both phototropism and chloroplast relocation

    PubMed Central

    Sakai, Tatsuya; Kagawa, Takatoshi; Kasahara, Masahiro; Swartz, Trevor E.; Christie, John M.; Briggs, Winslow R.; Wada, Masamitsu; Okada, Kiyotaka

    2001-01-01

    UV-A/blue light acts to regulate a number of physiological processes in higher plants. These include light-driven chloroplast movement and phototropism. The NPH1 gene of Arabidopsis encodes an autophosphorylating protein kinase that functions as a photoreceptor for phototropism in response to low-intensity blue light. However, nph1 mutants have been reported to exhibit normal phototropic curvature under high-intensity blue light, indicating the presence of an additional phototropic receptor. A likely candidate is the nph1 homologue, npl1, which has recently been shown to mediate the avoidance response of chloroplasts to high-intensity blue light in Arabidopsis. Here we demonstrate that npl1, like nph1, noncovalently binds the chromophore flavin mononucleotide (FMN) within two specialized PAS domains, termed LOV domains. Furthermore, when expressed in insect cells, npl1, like nph1, undergoes light-dependent autophosphorylation, indicating that npl1 also functions as a light receptor kinase. Consistent with this conclusion, we show that a nph1npl1 double mutant exhibits an impaired phototropic response under both low- and high-intensity blue light. Hence, npl1 functions as a second phototropic receptor under high fluence rate conditions and is, in part, functionally redundant to nph1. We also demonstrate that both chloroplast accumulation in response to low-intensity light and chloroplast avoidance movement in response to high-intensity light are lacking in the nph1npl1 double mutant. Our findings therefore indicate that nph1 and npl1 show partially overlapping functions in two different responses, phototropism and chloroplast relocation, in a fluence rate-dependent manner. PMID:11371609

  14. Gene profiling of the red light signalling pathways in roots.

    PubMed

    Molas, Maria Lia; Kiss, John Z; Correll, Melanie J

    2006-01-01

    Red light, acting through the phytochromes, controls numerous aspects of plant development. Many of the signal transduction elements downstream of the phytochromes have been identified in the aerial portions of the plant; however, very few elements in red-light signalling have been identified specifically for roots. Gene profiling studies using microarrays and quantitative Real-Time PCR were performed to characterize gene expression changes in roots of Arabidopsis seedlings exposed to 1 h of red light. Several factors acting downstream of phytochromes in red-light signalling in roots were identified. Some of the genes found to be differentially expressed in this study have already been characterized in the red-light-signalling pathway for whole plants. For example, PHYTOCHROME KINASE 1 (PKS1), LONG HYPOCOTYL 5 (HY5), EARLY FLOWERING 4 (ELF4), and GIGANTEA (GI) were all significantly up-regulated in roots of seedlings exposed to 1 h of red light. The up-regulation of SUPPRESSOR OF PHYTOCHROME A RESPONSES 1 (SPA1) and CONSTITUTIVE PHOTOMORPHOGENIC 1-like (COP1-like) genes suggests that the PHYA-mediated pathway was attenuated by red light. In addition, genes involved in lateral root and root hair formation, root plastid development, phenylpropanoid metabolism, and hormone signalling were also regulated by exposure to red light. Interestingly, members of the RPT2/NPH3 (ROOT PHOTOTROPIC 2/NON PHOTOTROPIC HYPOCOTYL 3) family, which have been shown to mediate blue-light-induced phototropism, were also differentially regulated in roots in red light. Therefore, these results suggest that red and blue light pathways interact in roots of seedlings and that many elements involved in red-light-signalling found in the aerial portions of the plant are differentially expressed in roots within 1 h of red light exposure.

  15. Phototropism and gravitropism in transgenic lines of Arabidopsis altered in the phytochrome pathway.

    PubMed

    Hopkins, Jane A; Kiss, John Z

    2012-07-01

    Phytochromes are a family of photoreceptor molecules, absorbing primarily in red and far-red, that are important in many aspects of plant development. These studies investigated the role of phytochromes in phototropism and gravitropism of seedlings of Arabidopsis thaliana. We used two transgenic lines, one which lacked phytochromes specifically in the roots (M0062/UASBVR) and the other lacked phytochromes in the shoots (CAB3::pBVR). These transgenic plants are deficient in the phytochrome chromophore in specific tissues due the expression of biliverdin IXa reductase (BVR), which binds to precursors of the chromophore. Experiments were performed in both light and dark conditions to determine whether roots directly perceive light signals or if the signal is perceived in the shoot and then transmitted to the root during tropistic curvature. Kinetics of tropisms and growth were assayed by standard methods or with a computer-based feedback system. We found that the perception of red light occurs directly in the root during phototropism in this organ and that signaling also may occur from root to shoot in gravitropism. Copyright © Physiologia Plantarum 2012.

  16. Blue and green light-induced phototropism in Arabidopsis thaliana and Lactuca sativa L. seedlings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steinitz, B.; Ren, Z.; Poff, K.L.

    1985-01-01

    Exposure time-response curves for blue and green light-induced phototropic bending in hypocotyls of Arabidopsis thaliana (L.) Heynh. and Lactuca sativa L. seedlings are presented. These seedlings show significant phototropic sensitivity up to 540 to 550 nanometers. Since wavelengths longer than 560 nanometers do not induce phototropic bending, it is suggested that the response to 510 to 550 nanometers light is mediated by the specific blue light photoreceptor of phototropism. The authors advise care in the use of green safelights for studies of phototropism.

  17. Blue-light regulation of ZmPHOT1 and ZmPHOT2 gene expression and the possible involvement of Zmphot1 in phototropism in maize coleoptiles.

    PubMed

    Suzuki, Hiromi; Okamoto, Ai; Kojima, Akane; Nishimura, Takeshi; Takano, Makoto; Kagawa, Takatoshi; Kadota, Akeo; Kanegae, Takeshi; Koshiba, Tomokazu

    2014-08-01

    ZmPHOT1 and ZmPHOT2 are expressed differentially in maize coleoptiles and leaves, with Zmphot1 possibly involved in first-positive phototropic curvature of red-light-adapted maize coleoptiles exposed to pulsed low-fluence blue light. Unilateral blue-light perception by phototropin(s) is the first event of phototropism, with the subsequent signal causing lateral transport of auxin at the coleoptile tip region of monocots. In this study, we analyzed the behavior of two maize phototropin genes: ZmPHOT1 and ZmPHOT2, the latter identified from the maize genome database and newly characterized. Quantitative real-time PCR analysis demonstrated that ZmPHOT1 was abundantly expressed in etiolated coleoptiles, while lower expressions of both ZmPHOT1 and ZmPHOT2 were observed in young leaves. Interestingly, these genes were not specifically expressed in the coleoptile tip region, a key position for photoperception in phototropism. Exposure to pulsed low-fluence blue light (LBL) (0.33 µmol m(-2) s(-1) × 8 s) and continuous high-fluence blue light (HBL) (10 µmol m(-2) s(-1)) rapidly decreased ZmPHOT1 gene expression in coleoptiles, with levels of ZmPHOT2 not significantly altered in that tissue. In young leaves, no drastic expression changes were induced in either ZmPHOT1 or ZmPHOT2 by LBL or HBL irradiation. The Zmphot1 protein was investigated by Western blot analysis with anti-Osphot1 antibodies. Zmphot1 was detected in microsomal fractions, with higher levels in coleoptiles than in leaves. HBL caused rapid phosphorylation of the protein, whereas no phot1 phosphorylation was induced by LBL. The involvement of Zmphot1 in LBL-induced phototropic curvature of maize coleoptiles is discussed.

  18. THE DEVELOPMENT OF A PHOTOTROPIC ANODIZED ALUMINUM FINISH RESPONSIVE TO GAMMA RADIATION.

    DTIC Science & Technology

    The present investigation was conducted to establish a phototropic anodized aluminum finish sensitive to gamma radiation. A comprehensive literature...search revealed a number of candidate phototropic materials but very little information about gamma radiation response. Because early trials...indicated that each candidate phototropic system possessed different dyeing characteristics for an anodic film, time-consuming trials with dyed anodic films

  19. A novel phototropic response to red light is revealed in microgravity.

    PubMed

    Millar, Katherine D L; Kumar, Prem; Correll, Melanie J; Mullen, Jack L; Hangarter, Roger P; Edelmann, Richard E; Kiss, John Z

    2010-05-01

    The aim of this study was to investigate phototropism in plants grown in microgravity conditions without the complications of a 1-g environment. Experiments performed on the International Space Station (ISS) were used to explore the mechanisms of both blue-light- and red-light-induced phototropism in plants. This project utilized the European Modular Cultivation System (EMCS), which has environmental controls for plant growth as well as centrifuges for gravity treatments used as a 1-g control. Images captured from video tapes were used to analyze the growth, development, and curvature of Arabidopsis thaliana plants that developed from seed in space. A novel positive phototropic response to red light was observed in hypocotyls of seedlings that developed in microgravity. This response was not apparent in seedlings grown on Earth or in the 1-g control during the space flight. In addition, blue-light-based phototropism had a greater response in microgravity compared with the 1-g control. Although flowering plants are generally thought to lack red light phototropism, our data suggest that at least some flowering plants may have retained a red light sensory system for phototropism. Thus, this discovery may have important implications for understanding the evolution of light sensory systems in plants.

  20. Blue and Green Light-Induced Phototropism in Arabidopsis thaliana and Lactuca sativa L. Seedlings 1

    PubMed Central

    Steinitz, Benjamin; Ren, Zhangling; Poff, Kenneth L.

    1985-01-01

    Exposure time-response curves for blue and green light-induced phototropic bending in hypocotyls of Arabidopsis thaliana (L.) Heynh. and Lactuca sativa L. seedlings are presented. These seedlings show significant phototropic sensitivity up to 540 to 550 nanometers. Since wave-lengths longer than 560 nanometers do not induce phototropic bending, it is suggested that the response to 510 to 550 nanometers light is mediated by the specific blue light photoreceptor of phototropism. We advise care in the use of green `safelights' for studies of phototropism. PMID:16664021

  1. Proper PIN1 Distribution Is Needed for Root Negative Phototropism in Arabidopsis

    PubMed Central

    Zhang, Kun-Xiao; Xu, Heng-Hao; Gong, Wen; Jin, Yan; Shi, Ya-Ya; Yuan, Ting-Ting; Li, Juan; Lu, Ying-Tang

    2014-01-01

    Plants can be adapted to the changing environments through tropic responses, such as light and gravity. One of them is root negative phototropism, which is needed for root growth and nutrient absorption. Here, we show that the auxin efflux carrier PIN-FORMED (PIN) 1 is involved in asymmetric auxin distribution and root negative phototropism. In darkness, PIN1 is internalized and localized to intracellular compartments; upon blue light illumination, PIN1 relocalize to basal plasma membrane in root stele cells. The shift of PIN1 localization induced by blue light is involved in asymmetric auxin distribution and root negative phototropic response. Both blue-light-induced PIN1 redistribution and root negative phototropism is mediated by a BFA-sensitive trafficking pathway and the activity of PID/PP2A. Our results demonstrate that blue-light-induced PIN1 redistribution participate in asymmetric auxin distribution and root negative phototropism. PMID:24465665

  2. Proper PIN1 distribution is needed for root negative phototropism in Arabidopsis.

    PubMed

    Zhang, Kun-Xiao; Xu, Heng-Hao; Gong, Wen; Jin, Yan; Shi, Ya-Ya; Yuan, Ting-Ting; Li, Juan; Lu, Ying-Tang

    2014-01-01

    Plants can be adapted to the changing environments through tropic responses, such as light and gravity. One of them is root negative phototropism, which is needed for root growth and nutrient absorption. Here, we show that the auxin efflux carrier PIN-FORMED (PIN) 1 is involved in asymmetric auxin distribution and root negative phototropism. In darkness, PIN1 is internalized and localized to intracellular compartments; upon blue light illumination, PIN1 relocalize to basal plasma membrane in root stele cells. The shift of PIN1 localization induced by blue light is involved in asymmetric auxin distribution and root negative phototropic response. Both blue-light-induced PIN1 redistribution and root negative phototropism is mediated by a BFA-sensitive trafficking pathway and the activity of PID/PP2A. Our results demonstrate that blue-light-induced PIN1 redistribution participate in asymmetric auxin distribution and root negative phototropism.

  3. Interaction between gravitropism and phototropism in sporangiophores of Phycomyces blakesleeanus.

    PubMed

    Grolig, F; Eibel, P; Schimek, C; Schapat, T; Dennison, D S; Galland, P A

    2000-06-01

    The interaction between gravitropism and phototropism was analyzed for sporangiophores of Phycomyces blakesleeanus. Fluence rate-response curves for phototropism were generated under three different conditions: (a) for stationary sporangiophores, which reached photogravitropic equilibrium; (b) for sporangiophores, which were clinostated head-over during phototropic stimulation; and (c) for sporangiophores, which were subjected to centrifugal accelerations of 2.3g to 8.4g. For blue light (454 nm), clinostating caused an increase of the slope of the fluence rate-response curves and an increase of the maximal bending angles at saturating fluence rates. The absolute threshold remained, however, practically unaffected. In contrast to the results obtained with blue light, no increase of the slope of the fluence rate-response curves was obtained with near-ultraviolet light at 369 nm. Bilateral irradiation with near-ultraviolet or blue light enhanced gravitropism, whereas symmetric gravitropic stimulation caused a partial suppression of phototropism. Gravitropism and phototropism appear to be tightly linked by a tonic feedback loop that allows the respective transduction chains a mutual influence over each other. The use of tropism mutants allowed conclusions to be drawn about the tonic feedback loop with the gravitropic and phototropic transduction chains. The results from clinostating mutants that lack octahedral crystals (implicated as statoliths) showed that these crystals are not involved in the tonic feedback loop. At elevated centrifugal accelerations, the fluence-rate-response curves for photogravitropic equilibrium were displaced to higher fluence rates and the slope decreased. The results indicate that light transduction possesses a logarithmic transducer, whereas gravi-transduction uses a linear one.

  4. Asymmetric distribution of auxin correlates with gravitropism and phototropism but not with autostraightening (autotropism) in pea epicotyls.

    PubMed

    Haga, Ken; Iino, Moritoshi

    2006-01-01

    The relationships between the distribution of the native auxin indole-3-acetic acid (IAA) and tropisms in the epicotyl of red light-grown pea (Pisum sativum L.) seedlings have been investigated. The distribution measurement was made in a defined zone of the third internode, using (3)H-IAA applied from the plumule as a tracer. The tropisms investigated were gravitropism, pulse-induced phototropism, and time-dependent phototropism. The investigation was extended to the phase of autostraightening (autotropism) that followed gravitropic curvature. It was found that IAA is asymmetrically distributed between the two halves of the zone, with a greater IAA level occurring on the convex side, at early stages of gravitropic and phototropic curvatures. This asymmetry was found in epidermal peels and, except for one case (pulse-induced phototropism), no asymmetry was detected in whole tissues. It was concluded, in support of earlier results, that auxin asymmetry mediates gravitropism and phototropism and that the epidermis or peripheral cell layers play an important role in the establishment of auxin asymmetry in pea epicotyls. During autostraightening, which results from a reversal of growth asymmetry, the extent of IAA asymmetry was reduced, but its direction was not reversed. This result demonstrated that autostraightening is not regulated through auxin distribution. In this study, the growth on either side of the investigated zone was also measured. In some cases, the measured IAA distribution could not adequately explain the local growth rate, necessitating further detailed investigation.

  5. Topology of an intracellular transduction chain (phototropism of Phycomyces): 1. Joint review of functional, temporal, and spatial aspects.

    PubMed

    Wenzler, D; Reinhardt, M; Fukshansky, L

    2001-08-21

    Two light-induced growth reactions in a unicellular cylindrical sporangiophore of Phycomyces blakesleeanus-vertical growth acceleration under symmetrical irradiation (photomecism) and directional growth under unilateral irradiation (phototropism)-share common input light perception as well as common output growth mechanism but have strongly divergent dynamics and other distinctive features. This divergence culminates in the phototropic paradoxes the main of which states that photomecism shows total adaptation, while phototropism does not adapt. The basis for this contradiction is that the phototropic transduction chain, unlike that of photomecism, faces a spatially non-uniform stimulus and processes a series of spatial patterns (light and absorption profiles, adaptation profile, etc.). The only way to resolve the paradoxes and correlate features of both responses within a single transduction chain is to assume non-local signal transduction, e.g. a cross-talk between different azimuthal locations within the cylindrical cell. On the other hand, to establish the presence of an appropriate cross-talk is equivalent of gaining insight into the topology of the transduction chain. This series of two papers contains a review reconsidering the entire field from this viewpoint (Paper 1) and a mathematical model of pattern transduction which unifies features of phototropism and resolves the paradoxes (Paper 2). At the same time, this is the first "proof of concept" for the "activity/pooling (a/p) networks"-a specific mathematical apparatus designed to analyse systemic properties and control in metabolic pathways. Copyright 2001 Academic Press.

  6. A novel blue-light phototropic response is revealed in roots of Arabidopsis thaliana in microgravity.

    PubMed

    Vandenbrink, Joshua P; Herranz, Raul; Medina, F Javier; Edelmann, Richard E; Kiss, John Z

    2016-12-01

    Blue-light positive phototropism in roots is masked by gravity and revealed in conditions of microgravity. In addition, the magnitude of red-light positive phototropic curvature is correlated to the magnitude of gravity. Due to their sessile nature, plants utilize environmental cues to grow and respond to their surroundings. Two of these cues, light and gravity, play a substantial role in plant orientation and directed growth movements (tropisms). However, very little is currently known about the interaction between light- (phototropic) and gravity (gravitropic)-mediated growth responses. Utilizing the European Modular Cultivation System on board the International Space Station, we investigated the interaction between phototropic and gravitropic responses in three Arabidopsis thaliana genotypes, Landsberg wild type, as well as mutants of phytochrome A and phytochrome B. Onboard centrifuges were used to create a fractional gravity gradient ranging from reduced gravity up to 1g. A novel positive blue-light phototropic response of roots was observed during conditions of microgravity, and this response was attenuated at 0.1g. In addition, a red-light pretreatment of plants enhanced the magnitude of positive phototropic curvature of roots in response to blue illumination. In addition, a positive phototropic response of roots was observed when exposed to red light, and a decrease in response was gradual and correlated with the increase in gravity. The positive red-light phototropic curvature of hypocotyls when exposed to red light was also confirmed. Both red-light and blue-light phototropic responses were also shown to be affected by directional light intensity. To our knowledge, this is the first characterization of a positive blue-light phototropic response in Arabidopsis roots, as well as the first description of the relationship between these phototropic responses in fractional or reduced gravities.

  7. A novel blue-light phototropic response is revealed in roots of Arabidopsis thaliana in microgravity

    PubMed Central

    Vandenbrink, Joshua P.; Herranz, Raul; Medina, F. Javier; Edelmann, Richard E.

    2017-01-01

    Main conclusion Blue-light positive phototropism in roots is masked by gravity and revealed in conditions of microgravity. In addition, the magnitude of red-light positive phototropic curvature is correlated to the magnitude of gravity. Due to their sessile nature, plants utilize environmental cues to grow and respond to their surroundings. Two of these cues, light and gravity, play a substantial role in plant orientation and directed growth movements (tropisms). However, very little is currently known about the interaction between light- (phototropic) and gravity (gravitropic)-mediated growth responses. Utilizing the European Modular Cultivation System on board the International Space Station, we investigated the interaction between phototropic and gravitropic responses in three Arabidopsis thaliana genotypes, Landsberg wild type, as well as mutants of phytochrome A and phytochrome B. Onboard centrifuges were used to create a fractional gravity gradient ranging from reduced gravity up to 1g. A novel positive blue-light phototropic response of roots was observed during conditions of microgravity, and this response was attenuated at 0.1g. In addition, a red-light pretreatment of plants enhanced the magnitude of positive phototropic curvature of roots in response to blue illumination. In addition, a positive phototropic response of roots was observed when exposed to red light, and a decrease in response was gradual and correlated with the increase in gravity. The positive red-light phototropic curvature of hypocotyls when exposed to red light was also confirmed. Both red-light and blue-light phototropic responses were also shown to be affected by directional light intensity. To our knowledge, this is the first characterization of a positive blue-light phototropic response in Arabidopsis roots, as well as the first description of the relationship between these phototropic responses in fractional or reduced gravities. PMID:27507239

  8. Role of carotenoids in the phototropic response of corn seedings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vierstra, R.D.; Poff, K.L.

    1981-10-01

    The herbicide 4 chloro-5-(methylamino)-2-..cap alpha..,..cap alpha..,..cap alpha..,-trifluoro-m-tolyl)-3(2H)- pyridazinone (SAN 9789), which blocks the synthesis in higher plants of colored carotenoids but not of flavins, was used to examine the involvement of carotenoids in corn seeding phototropism. It was concluded that ''bulk'' carotenoids are not the photoreceptor pigment based on the results that increasing concentrations of SAN 9789 (up to 100 micromolar) did not alter the phototropic sensitivity to 380 nanometers light (using geotropism as a control) and did not increase the threshold intensities of fluence response curves for both 380 and 450 nanometers light even though carotenoid content was reducedmore » to 1 to 2% of normal. SAN 9789 treatment, however, did reduce seedling sensitivity toward 450 nanometers light indicating that carotenoids are involved in phototropism. Carotenoids, which are located mainly in the primary leaves, may act in phototropism as an internal screen, enhancing the light intensity gradient across the seedling and thus contributing to the ability of the seedling to perceive light direction. These results, indicate that the action spectra for phototropic responses can be significantly affected by the absorbance of screening pigments in vivo thus altering its shape from the in vitro absorption spectrum of the photoreceptor pigment.« less

  9. Dynamic near-infrared imaging reveals transient phototropic change in retinal rod photoreceptors.

    PubMed

    Lu, Rongwen; Levy, Alexander M; Zhang, Qiuxiang; Pittler, Steven J; Yao, Xincheng

    2013-10-01

    Stiles-Crawford effect (SCE) is exclusively observed in cone photoreceptors, but why the SCE is absent in rod photoreceptors is still a mystery. In this study, we employed dynamic near infrared light imaging to monitor photoreceptor kinetics in freshly isolated frog and mouse retinas stimulated by oblique visible light flashes. It was observed that retinal rods could rapidly (onset: ∼10 ms for frog and 5 ms for mouse; time-to-peak: ∼200 ms for frog and 30 ms for mouse) shift toward the direction of the visible light, which might quickly compensate for the loss of luminous efficiency due to oblique illumination. In contrast, such directional movement was negligible in retinal cones. Moreover, transient rod phototropism could contribute to characteristic intrinsic optical signal (IOS). We anticipate that further study of the transient rod phototropism may not only provide insight into better understanding of the nature of vision but also promise an IOS biomarker for functional mapping of rod physiology at high resolution.

  10. THE DYNACELL AND FOCAL PLANE CONCEPTS OF PHOTOTROPIC SYSTEMS APPLICATION TO OPHTHALMIC NUCLEAR FLASH-PROTECTIVE DEVICES

    DTIC Science & Technology

    Two concepts of phototropic systems application are presented in this report. These concepts, when considered individually or in combination, make...possible the development of improved, directly or indirectly actuated, phototropic , ophthalmic, nuclear flash-protective devices. By the application...of a phototropic filter at the focal plane of an optical system, the attenuation of the phototropic response due to distance is minimized. Using a

  11. Interaction between Gravitropism and Phototropism in Sporangiophores of Phycomyces blakesleeanus1

    PubMed Central

    Grolig, Franz; Eibel, Peter; Schimek, Christine; Schapat, Tanja; Dennison, David S.; Galland, Paul A.

    2000-01-01

    The interaction between gravitropism and phototropism was analyzed for sporangiophores of Phycomyces blakesleeanus. Fluence rate-response curves for phototropism were generated under three different conditions: (a) for stationary sporangiophores, which reached photogravitropic equilibrium; (b) for sporangiophores, which were clinostated head-over during phototropic stimulation; and (c) for sporangiophores, which were subjected to centrifugal accelerations of 2.3g to 8.4g. For blue light (454 nm), clinostating caused an increase of the slope of the fluence rate-response curves and an increase of the maximal bending angles at saturating fluence rates. The absolute threshold remained, however, practically unaffected. In contrast to the results obtained with blue light, no increase of the slope of the fluence rate-response curves was obtained with near-ultraviolet light at 369 nm. Bilateral irradiation with near-ultraviolet or blue light enhanced gravitropism, whereas symmetric gravitropic stimulation caused a partial suppression of phototropism. Gravitropism and phototropism appear to be tightly linked by a tonic feedback loop that allows the respective transduction chains a mutual influence over each other. The use of tropism mutants allowed conclusions to be drawn about the tonic feedback loop with the gravitropic and phototropic transduction chains. The results from clinostating mutants that lack octahedral crystals (implicated as statoliths) showed that these crystals are not involved in the tonic feedback loop. At elevated centrifugal accelerations, the fluence-rate-response curves for photogravitropic equilibrium were displaced to higher fluence rates and the slope decreased. The results indicate that light transduction possesses a logarithmic transducer, whereas gravi-transduction uses a linear one. PMID:10859206

  12. Root phototropism: how light and gravity interact in shaping plant form

    NASA Technical Reports Server (NTRS)

    Kiss, John Z.; Correll, Melanie J.; Mullen, Jack L.; Hangarter, Roger P.; Edelmann, Richard E.

    2003-01-01

    The interactions among tropisms can be critical in determining the final growth form of plants and plant organs. We have studied tropistic responses in roots as an example of these type of interactions. While gravitropism is the predominant tropistic response in roots, phototropism also plays a role in the oriented growth in this organ in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism. In the flowering plant Arabidopsis, the photosensitive pigments phytochrome A (phyA) and phytochrome B (phyB) mediate this positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. While blue-light-based negative phototropism is primarily mediated by the phototropin family of photoreceptors, the phyA and phyAB mutants (but not phyB) were inhibited in this response relative to the WT. The differences observed in phototropic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in plants and that phytochrome plays a key role in integrating multiple environmental stimuli.

  13. Root phototropism: how light and gravity interact in shaping plant form.

    PubMed

    Kiss, John Z; Correll, Melanie J; Mullen, Jack L; Hangarter, Roger P; Edelmann, Richard E

    2003-06-01

    The interactions among tropisms can be critical in determining the final growth form of plants and plant organs. We have studied tropistic responses in roots as an example of these type of interactions. While gravitropism is the predominant tropistic response in roots, phototropism also plays a role in the oriented growth in this organ in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism. In the flowering plant Arabidopsis, the photosensitive pigments phytochrome A (phyA) and phytochrome B (phyB) mediate this positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. While blue-light-based negative phototropism is primarily mediated by the phototropin family of photoreceptors, the phyA and phyAB mutants (but not phyB) were inhibited in this response relative to the WT. The differences observed in phototropic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in plants and that phytochrome plays a key role in integrating multiple environmental stimuli.

  14. Mechanism of specific inhibition of phototropism by phenylacetic acid in corn seedling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vierstra, R.D.; Poff, K.L.

    1981-05-01

    Using geotropism as a control for phototropism, compounds similar to phenylacetic acid that phototreact with flavins and/or have auxin-like activity were examined for their ability to specifically inhibit phototropism in corn seedlings using geotropism as a control. Results using indole-3-acetic acid, napthalene-1-acetic acid, naphthalene-2-acetic acid, phenylacetic acid, and ..beta..-phenylpyruvic acid suggest that such compounds will specifically inhibit phototropism primarily because of their photoreactivity with flavins and not their auxin activity. In addition, the in vivo concentration of phenylacetic acid required to induce specificity was well below that required to stimulate coleoptile growth. Estimates of the percentage of photoreceptor pigment inactivatedmore » by phenylacetic acid (>10%) suggest that phenylacetic acid could be used to photoaffinity label the flavoprotein involved in corn seedling phototropism.« less

  15. Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Janoudi, A. K.; Poff, K. L.

    1993-01-01

    Phototropism is induced by blue light, which also induces desensitization, a partial or total loss of phototropic responsiveness. The fluence and fluence-rate dependence of desensitization and recovery from desensitization have been measured for etiolated and red light (669-nm) preirradiated Arabidopsis thaliana seedlings. The extent of desensitization increased as the fluence of the desensitizing 450-nm light was increased from 0.3 to 60 micromoles m-2 s-1. At equal fluences, blue light caused more desensitization when given at a fluence rate of 1.0 micromole m-2 s-1 than at 0.3 micromole m-2 s-1. In addition, seedlings irradiated with blue light at the higher fluence rate required a longer recovery time than seedlings irradiated at the lower fluence rate. A red light preirradiation, probably mediated via phytochrome, decreased the time required for recovery from desensitization. The minimum time for detectable recovery was about 65 s, and the maximum time observed was about 10 min. It is proposed that the descending arm of the fluence-response relationship for first positive phototropism is a consequence of desensitization, and that the time threshold for second positive phototropism establishes a period during which recovery from desensitization occurs.

  16. Mutants of Arabidopsis thaliana with decreased amplitude in their phototropic response

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khurana, J.P.; Ren, Zhangling; Steinitz, B.

    1989-10-01

    Two mutants of Arabidopsis thaliana have been identified with decreased phototropism to 450-nanometer light. Fluence-response relationships for these strains (ZR8 and ZR19) to single and multiple flashes of light show thresholds, curve shapes, and fluence for maximum curvature in first positive phototropism which are the same as those of the wild type. Similarly, there is no alteration from the wild type in the kinetics of curvature or in the optimum dark period separating sequential flashes in a multiple flash regimen. In addition, in both strains, gravitropism is decreased compared to the wild type by an amount which is comparable tomore » the decrease in phototropism. Based on reciprocal backcrosses, it appears that the alteration is due to a recessive nuclear mutation. It is suggested that ZR8 and ZR19 represent alterations in some step analogous to an amplifier, downstream of the photoreceptor pigment, and common to both phototropism and gravitropism.« less

  17. Mutants of Arabidopsis thaliana with decreased amplitude in their phototropic response

    NASA Technical Reports Server (NTRS)

    Khurana, J. P.; Ren, Z.; Steinitz, B.; Parks, B.; Best, T. R.; Poff, K. L.

    1989-01-01

    Two mutants of Arabidopsis thaliana have been identified with decreased phototropism to 450-nanometer light. Fluence-response relationships for these strains (ZR8 and ZR19) to single and multiple flashes of light show thresholds, curve shapes, and fluence for maximum curvature in first positive' phototropism which are the same as those of the wild type. Similarly, there is no alteration from the wild type in the kinetics of curvature or in the optimum dark period separating sequential flashes in a multiple flash regimen. In addition, in both strains, gravitropism is decreased compared to the wild type by an amount which is comparable to the decrease in phototropism. Based on reciprocal backcrosses, it appears that the alteration is due to a recessive nuclear mutation. It is suggested that ZR8 and ZR19 represent alterations in some step analogous to an amplifier, downstream of the photoreceptor pigment, and common to both phototropism and gravitropism.

  18. Anisotropic plant growth due to phototropism.

    PubMed

    Pietruszka, M; Lewicka, S

    2007-01-01

    Phototropism--the directional curvature of organs in response to lateral differences in light intensity and/or quality--represents one of the most rapid and visually obvious reaction of plants to changes in their light environment. It is a topic of fundamental interest to understand the mechanics of plants during growth. We propose a generalization of the scalar Lockhart model (1965) to three dimensional deformation, solve the new equation in two particular cases and compare results with empirical data. We believe that carefully designed experiments linked to our model will provide (by determining the active transport coefficient) a new method for qualitative description of auxin redistribution during phototropism. The proposed method supplements very recent investigations concerning specific auxin-influx and -efflux carriers (LAX and PIN proteins).

  19. Kinetic separation of phototropism from blue-light inhibition of stem elongation

    NASA Technical Reports Server (NTRS)

    Cosgrove, D. J.

    1985-01-01

    These experiments tested the hypothesis that phototropic bending arises when a light gradient across the stem differentially inhibits cell elongation because of direct inhibition of cell elongation by light (the Blaauw hypothesis). Continuous irradiation of dark-grown cucumber seedlings (Cucumis sativus L.) with unilateral blue light inhibited hypocotyl elongation within 30 s, but did not induce phototropic curvature until 4.5 h after the start of irradiation. Marking experiments showed that curvature began simultaneously at the top and bottom of the growing region. In situ measurements of the light gradient across the stem with a glass fiber optic indicated that a 5- to 6-fold difference in fluence rate was established on the two sides of the stem. The light gradient established at the start of irradiation was the same as that after 6 h of irradiation. Changes in gravitropic responsiveness during this period were also ruled out. Calculations show that the light gradient should have caused curvature which would be detectable within 30 to 60 min and which would extrapolate to the start of irradiation--if the Blaauw hypothesis were correct. The long lag for phototropism in this case indicates that rapid inhibition of cell elongation by blue light does not cause the asymmetrical growth of phototropism. Rather, phototropism is superimposed upon this separate light growth response.

  20. Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Janoudi, A.K.; Poff, K.L.

    1993-04-01

    Phototropism is induced by blue light, which also induces desensitization, a partial or total loss of phototropic responsiveness. The fluence and fluence-rate dependence of densensitization and recovery from desensitization have been measured for etiolated and red light (669-nm) preirradiated Arabidopsis thaliana seedlings. The extent of desensitization increased as the fluence of the desensitizing 450-nm light was increased from 0.3 to 60 [mu]mol m[sup [minus]2] s[sup [minus]1]. At equal fluences, blue light caused more desensitization when given at a fluence rate of 1.0 [mu]mol m[sup [minus]2] s[sup [minus]1] than at 0.3 [mu]mol m[sup [minus]2] s[sup [minus]1]. In addition, seedlings irradiated withmore » blue light at the higher fluence rate required a longer recovery time than seedlings irradiated at the lower fluence rate. A red light preirradiation, probably mediated via phytochrome, decreased the time required for recovery from desensitization. The minimum time for detectable recovery was about 65 s, and the maximum time observed was about 10 min. It is proposed that the descending arm of the fluence-response relationship for first positive phototropism is a consequence of desensitization, and that the time threshold for second positive phototropism establishes a period during which recovery from desensitization occurs. 11 refs., 6 figs.« less

  1. Kinetics for phototropic curvature by etiolated seedlings of Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Orbovic, V.; Poff, K. L.

    1991-01-01

    An infrared-imaging system has been used to study the influence of gravity on the kinetics of first positive phototropism. The development of phototropic curvature of etiolated seedlings of Arabidopsis thaliana was measured in the absence of visible radiation. Following a pulse of blue light, stationary seedlings curved to a maximum of approximately 16 degrees about 80 minutes after stimulation. The seedlings then curved upward again or straightened by about 6 degrees during the subsequent 100 minutes. Seedlings rotated on a clinostat reached a similar maximum curvature following photostimulation. These seedlings maintained that curvature for 30 to 40 minutes before subsequently straightening to the same extent as the stationary seedlings. It is concluded that straightening is not a consequence of gravitropism, although gravity has some effect on the phototropism kinetics.

  2. Phytochromes play a role in phototropism and gravitropism in Arabidopsis roots.

    PubMed

    Correll, Melanie J; Coveney, Katrina M; Raines, Steven V; Mullen, Jack L; Hangarter, Roger P; Kiss, John Z

    2003-01-01

    Phototropism as well as gravitropism plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. Phytochrome A (phyA) and phyB mediate the positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. In blue-light-based negative phototropism, phyA and phyAB (but not phyB) were inhibited in the response relative to the WT. In root gravitropism, phyB and phyAB (but not phyA) were inhibited in the response compared to the WT. The differences observed in tropistic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in roots and that phytochrome plays a key role in plant development by integrating multiple environmental stimuli. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  3. Phytochromes play a role in phototropism and gravitropism in Arabidopsis roots

    NASA Astrophysics Data System (ADS)

    Correll, Melanie J.; Coveney, Katrina M.; Raines, Steven V.; Mullen, Jack L.; Hangarter, Roger P.; Kiss, John Z.

    2003-05-01

    Phototropism as well as gravitropism plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. Phytochrome A (phyA) and phyB mediate the positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. In blue-light-based negative phototropism, phyA and phyAB (but not phyB) were inhibited in the response relative to the WT. In root gravitropism, phyB and phyAB (but not phyA) were inhibited in the response compared to the WT. The differences observed in tropistic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in roots and that phytochrome plays a key role in plant development by integrating multiple environmental stimuli.

  4. Phytochromes play a role in phototropism and gravitropism in Arabidopsis roots

    NASA Technical Reports Server (NTRS)

    Correll, Melanie J.; Coveney, Katrina M.; Raines, Steven V.; Mullen, Jack L.; Hangarter, Roger P.; Kiss, John Z.

    2003-01-01

    Phototropism as well as gravitropism plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. Phytochrome A (phyA) and phyB mediate the positive red-light-based photoresponse in roots since single mutants (and the double phyAB mutant) were severely impaired in this response. In blue-light-based negative phototropism, phyA and phyAB (but not phyB) were inhibited in the response relative to the WT. In root gravitropism, phyB and phyAB (but not phyA) were inhibited in the response compared to the WT. The differences observed in tropistic responses were not due to growth limitations since the growth rates among all the mutants tested were not significantly different from that of the WT. Thus, our study shows that the blue-light and red-light systems interact in roots and that phytochrome plays a key role in plant development by integrating multiple environmental stimuli. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  5. Defining the site of light perception and initiation of phototropism in Arabidopsis.

    PubMed

    Preuten, Tobias; Hohm, Tim; Bergmann, Sven; Fankhauser, Christian

    2013-10-07

    Phototropism is an adaptive response allowing plants to optimize photosynthetic light capture. This is achieved by asymmetric growth between the shaded and lit sides of the stimulated organ. In grass seedlings, the site of phototropin-mediated light perception is distinct from the site of bending; however, in dicotyledonous plants (e.g., Arabidopsis), spatial aspects of perception remain debatable. We use morphological studies and genetics to show that phototropism can occur in the absence of the root, lower hypocotyl, hypocotyl apex, and cotyledons. Tissue-specific expression of the phototropin1 (phot1) photoreceptor demonstrates that light sensing occurs in the upper hypocotyl and that expression of phot1 in the hypocotyl elongation zone is sufficient to enable a normal phototropic response. Moreover, we show that efficient phototropism occurs when phot1 is expressed from endodermal, cortical, or epidermal cells and that its local activation rapidly leads to a global response throughout the seedling. We propose that spatial aspects in the steps leading from light perception to growth reorientation during phototropism differ between grasses and dicots. These results are important to properly interpret genetic experiments and establish a model connecting light perception to the growth response, including cellular and morphological aspects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Buder revisited: cell and organ polarity during phototropism.

    PubMed

    Nick, P; Furuya, M

    1996-10-01

    The induction of a radial polarity by environmental stimuli was studied at the cellular and organ levels, with phototropism chosen as a model. The light gradient acting on the whole coleoptile was opposed to the light direction acting upon individual cells in the classical Buder experiment, irradiating from the inside out. Alternatively, the stimulus was administered to the coleoptile tip with a microbeam-irradiation device. Tropistic curvature was assayed as a marker for the response of the whole organ, whereas cell elongation and the orientation of cortical microtubules were taken as markers for the responses of individual cells. Upon tip irradiation, signals much faster than basipetal auxin transport migrate towards the base. The data are discussed in terms of an organ polarity that is the primary result of the asymmetric light signal and affects, in a second step, an endogenous radial polarity of epidermal cells.

  7. Phototropism of Arabidopsis thaliana in microgravity and fractional gravity on the International Space Station.

    PubMed

    Kiss, John Z; Millar, Katherine D L; Edelmann, Richard E

    2012-08-01

    While there is a great deal of knowledge regarding plant growth and development in microgravity aboard orbiting spacecraft, there is little information available about these parameters in reduced or fractional gravity conditions (less than the nominal 1g on Earth). Thus, in these experiments using the European Modular Cultivation System on the International Space Station, we studied the interaction between phototropism and gravitropism in the WT and mutants of phytochrome A and B of Arabidopis thaliana. Fractional gravity and the 1 g control were provided by centrifuges in the spaceflight hardware, and unidirectional red and blue illumination followed a white light growth period in the time line of the space experiments. The existence of red-light-based positive phototropism in hypocotyls of seedlings that is mediated by phytochrome was confirmed in these microgravity experiments. Fractional gravity studies showed an attenuation of red-light-based phototropism in both roots and hypocotyls of seedlings occurring due to gravitational accelerations ranging from 0.l to 0.3 g. In contrast, blue-light negative phototropism in roots, which was enhanced in microgravity compared with the 1g control, showed a significant attenuation at 0.3 g. In addition, our studies suggest that the well-known red-light enhancement of blue-light-induced phototropism in hypocotyls is likely due to an indirect effect by the attenuation of gravitropism. However, red-light enhancement of root blue-light-based phototropism may occur via a more direct effect on the phototropism system itself, most likely through the phytochrome photoreceptors. To our knowledge, these experiments represent the first to examine the behavior of flowering plants in fractional or reduced gravity conditions.

  8. INVESTIGATION OF INORGANIC PHOTOTROPIC MATERIALS AS A BI-OPTIC ELEMENT APPLICABLE IN HIGH DENSITY STORAGE COMPUTER MEMORIES

    DTIC Science & Technology

    A general valuation of the various types of phototropic (i.e., reversible, light induced, color producing) phenomenon is given regarding the...application of phototropic material to bioptic high density storage media for compu er memories. The inorganic ’’F’’ center type phototropic systems were

  9. Interaction of root gravitropism and phototropism in Arabidopsis wild-type and starchless mutants.

    PubMed

    Vitha, S; Zhao, L; Sack, F D

    2000-02-01

    Root gravitropism in wild-type Arabidopsis and in two starchless mutants, pgm1-1 and adg1-1, was evaluated as a function of light position to determine the relative strengths of negative phototropism and of gravitropism and how much phototropism affects gravitropic measurements. Gravitropism was stronger than phototropism in some but not all light positions in wild-type roots grown for an extended period, indicating that the relationship between the two tropisms is more complex than previously reported. Root phototropism significantly influenced the time course of gravitropic curvature and the two measures of sensitivity. Light from above during horizontal exposure overestimated all three parameters for all three genotypes except the wild-type perception time. At the irradiance used (80 micromol m(-2) s(-1)), the shortest periods of illumination found to exaggerate gravitropism were 45 min of continuous illumination and 2-min doses of intermittent illumination. By growing roots in circumlateral light or by gravistimulating in the dark, corrected values were obtained for each gravitropic parameter. Roots of both starchless mutants were determined to be about three times less sensitive than prior estimates. This study demonstrates the importance of accounting for phototropism in the design of root gravitropism experiments in Arabidopsis.

  10. Interaction of root gravitropism and phototropism in Arabidopsis wild-type and starchless mutants

    NASA Technical Reports Server (NTRS)

    Vitha, S.; Zhao, L.; Sack, F. D.

    2000-01-01

    Root gravitropism in wild-type Arabidopsis and in two starchless mutants, pgm1-1 and adg1-1, was evaluated as a function of light position to determine the relative strengths of negative phototropism and of gravitropism and how much phototropism affects gravitropic measurements. Gravitropism was stronger than phototropism in some but not all light positions in wild-type roots grown for an extended period, indicating that the relationship between the two tropisms is more complex than previously reported. Root phototropism significantly influenced the time course of gravitropic curvature and the two measures of sensitivity. Light from above during horizontal exposure overestimated all three parameters for all three genotypes except the wild-type perception time. At the irradiance used (80 micromol m(-2) s(-1)), the shortest periods of illumination found to exaggerate gravitropism were 45 min of continuous illumination and 2-min doses of intermittent illumination. By growing roots in circumlateral light or by gravistimulating in the dark, corrected values were obtained for each gravitropic parameter. Roots of both starchless mutants were determined to be about three times less sensitive than prior estimates. This study demonstrates the importance of accounting for phototropism in the design of root gravitropism experiments in Arabidopsis.

  11. Mechanism of Specific Inhibition of Phototropism by Phenylacetic Acid in Corn Seedling 1

    PubMed Central

    Vierstra, Richard D.; Poff, Kenneth L.

    1981-01-01

    Using geotropism as a control for phototropism, compounds similar to phenylacetic acid that photoreact with flavins and/or have auxin-like activity were examined for their ability to specifically inhibit phototropism in corn seedlings using geotropism as a control. Results using indole-3-acetic acid, napthalene-1-acetic acid, naphthalene-2-acetic acid, phenylacetic acid, and β-phenylpyruvic acid suggest that such compounds will specifically inhibit phototropism primarily because of their photoreactivity with flavins and not their auxin activity. For example, strong auxins, indole-3-acetic acid and naphthalene-1-acetic acid, affected both tropic responses at all concentrations tested whereas weak auxins, phenylacetic acid and naphthalene-2-acetic acid, exhibited specific inhibition. In addition, the in vivo concentration of phenylacetic acid required to induce specificity was well below that required to stimulate coleoptile growth. Estimates of the percentage of photoreceptor pigment inactivated by phenylacetic acid (>10%) suggest that phenylacetic acid could be used to photoaffinity label the flavoprotein involved in corn seedling phototropism. PMID:16661774

  12. Interaction of Root Gravitropism and Phototropism in Arabidopsis Wild-Type and Starchless Mutants1

    PubMed Central

    Vitha, Stanislav; Zhao, Liming; Sack, Fred David

    2000-01-01

    Root gravitropism in wild-type Arabidopsis and in two starchless mutants, pgm1-1 and adg1-1, was evaluated as a function of light position to determine the relative strengths of negative phototropism and of gravitropism and how much phototropism affects gravitropic measurements. Gravitropism was stronger than phototropism in some but not all light positions in wild-type roots grown for an extended period, indicating that the relationship between the two tropisms is more complex than previously reported. Root phototropism significantly influenced the time course of gravitropic curvature and the two measures of sensitivity. Light from above during horizontal exposure overestimated all three parameters for all three genotypes except the wild-type perception time. At the irradiance used (80 μmol m−2 s−1), the shortest periods of illumination found to exaggerate gravitropism were 45 min of continuous illumination and 2-min doses of intermittent illumination. By growing roots in circumlateral light or by gravistimulating in the dark, corrected values were obtained for each gravitropic parameter. Roots of both starchless mutants were determined to be about three times less sensitive than prior estimates. This study demonstrates the importance of accounting for phototropism in the design of root gravitropism experiments in Arabidopsis. PMID:10677438

  13. Phototropism experiments in microgravity-the Seedling Growth project in the EMCS on the ISS

    NASA Astrophysics Data System (ADS)

    Kiss, John; Edelmann, Richard; Herranz, Raul; Medina, Francisco Javier; Millar, Katherine

    The microgravity environment aboard orbiting spacecraft has provided a unique laboratory to explore important topics in basic plant biology. Our group has utilized the European Modular Cultivation System (EMCS) aboard the International Space Station (ISS) to study plant growth, development, tropisms, and gene expression in a series of spaceflight experiments. The most current project performed on the ISS was termed Seeding Growth-1 (SG-1) which builds on the previous TROPI (for tropisms) experiments. TROPI-1 was the first EMCS experiment, and we discovered a novel red-light-based phototropism in hypocotyls of seedlings grown in microgravity (Millar et al. 2010). In TROPI-2, our experiments were extended to reduced gravity levels and found that 0.1-0.3 g can attenuate the red-light response (Kiss et al. 2012). In addition, we performed gene profiling studies and noted that approximately 280 genes that were differentially regulated at least two-fold in the space samples compared to the ground controls (Correll et al. 2013). Major technical and operational changes in SG-1 (launched in March 2013) compared to the TROPI experiments include: improvements in lighting conditions within the EMCS to optimize the environment for phototropism studies and the use of infrared illumination to provide high-quality images of the seedlings. In SG-1, the red-light-based phototropism in roots and hypocotyls of seedlings that was noted in TROPI-2 was confirmed and now can be more precisely characterized based on the improvements in procedures. As we move forward, the SG-2 experiments (to be launched in 2014), in addition to a continued focus on phototropism, will consider the cell cycle as well as the growth and proliferation of plant cells in microgravity (Matía et al. 2010). Furthermore, the lessons learned from sequential experiments from TROPI-1 to TROPI-2 to SG-1 can provide insights to other researchers developing space experiments in plant biology. References: Correll M.J., T

  14. phot1 Inhibition of ABCB19 Primes Lateral Auxin Fluxes in the Shoot Apex Required For Phototropism

    PubMed Central

    Christie, John M.; Thomson, Catriona E.; Lin, Jinshan; Titapiwatanakun, Boosaree; Ennis, Margaret; Kaiserli, Eirini; Lee, Ok Ran; Adamec, Jiri; Peer, Wendy A.; Murphy, Angus S.

    2011-01-01

    It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperms. PMID:21666806

  15. phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism.

    PubMed

    Christie, John M; Yang, Haibing; Richter, Gregory L; Sullivan, Stuart; Thomson, Catriona E; Lin, Jinshan; Titapiwatanakun, Boosaree; Ennis, Margaret; Kaiserli, Eirini; Lee, Ok Ran; Adamec, Jiri; Peer, Wendy A; Murphy, Angus S

    2011-06-01

    It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperms.

  16. Both LOV1 and LOV2 domains of phototropin2 function as the photosensory domain for hypocotyl phototropic responses in Arabidopsis thaliana (Brassicaceae).

    PubMed

    Suetsugu, Noriyuki; Kong, Sam-Geun; Kasahara, Masahiro; Wada, Masamitsu

    2013-01-01

    Phototropins (phot) are blue light receptor proteins that mediate phototropism and control photomovement responses, such as chloroplast photorelocation movement and stomatal opening. Arabidopsis thaliana has two phototropins, phot1 and phot2. Although both phot1 and phot2 redundantly mediate photomovement responses, phot2 uniquely regulates phototropism and the chloroplast avoidance response under high-intensity blue light. However, compared to that of phot1, the mechanistic basis of phot2 function is poorly understood, and in particular, the importance of the LOV2 domain in phot2 function has not been clearly demonstrated. Indeed, photocycle-deficient LOV2 transgenic lines expressing phot2 in a phot1phot2 mutant background retained phototropism, although with less sensitivity than wild-type plants. We isolated 11 alleles of phot2 mutants and determined the molecular lesion in each allele. We analyzed hypocotyl phototropism, chloroplast photorelocation movement, and leaf flattening in the phot2 mutant and the respective phot1phot2 double mutant plants. We demonstrated that unlike the phot2 null mutant, the phot2-10 mutant, which has the defective phot2 LOV2 domain, retained the phototropic response and had unusual chloroplast movement. Mutants phot2-2 and phot2-6, which have a missense mutation in the kinase activation loop of phot2, had the phot2-null mutant phenotype. Furthermore, we convincingly demonstrated that the commonly used phot2-1 mutant allele is a phot2-null mutant. The analyses of the multiple phot2 mutant alleles provided strong evidence for the importance of both LOV domains and the kinase activation loop of phot2 in phototropism and other phot-dependent responses and also demonstrated that phot2-1 allele is a null mutant.

  17. Blue light-induced phototropism of inflorescence stems and petioles is mediated by phototropin family members phot1 and phot2.

    PubMed

    Kagawa, Takatoshi; Kimura, Mitsuhiro; Wada, Masamitsu

    2009-10-01

    Phototropin family photoreceptors, phot1 and phot2, in Arabidopsis thaliana control the blue light (BL)-mediated phototropic responses of the hypocotyl, chloroplast relocation movement and stomatal opening. Phototropic responses in dark-grown tissues have been well studied but those in de-etiolated green plants are not well understood. Here, we analyzed phototropic responses of inflorescence stems and petioles of wild-type and phototropin mutant plants of A. thaliana. Similar to the results obtained from dark-grown seedlings, inflorescence stems and petioles in wild-type and phot2 mutant plants showed phototropic bending towards low fluence BL, while in phot1 mutant plants, a high fluence rate of BL was required. phot1 phot2 double mutant plants did not show any phototropic responses even under very high fluence rates of BL. We further studied the photoreceptive sites for phototropic responses of stems and petioles by partial tissue irradiation. The whole part of the inflorescence stem is sensitive to BL and shows phototropism, but in the petiole only the irradiated abaxial side is sensitive. Similar to dark-grown etiolated seedlings, phot1 plays a major role in phototropic responses under weak light, but phot2 functions under high fluence rate conditions in green plants.

  18. Studying Phototropism Using a Small Growth Chamber.

    ERIC Educational Resources Information Center

    Fisher, Maryanna, F.; Llewellyn, Gerald C.

    1978-01-01

    Describes a simple and inexpensive way to construct two small growth chambers for studying phototropism in the science classroom. One chamber is designed to illustrate how plants grow around obstacles to reach light and the other to illustrate directional light responses. (HM)

  19. Gravitropism and phototropism of oat coleoptiles: post-tropic autostraightening and tissue shrinkage during tropism.

    PubMed

    Tarui, Y; Iino, M

    1999-01-01

    We measured changes in length on the two opposite sides of the red-light-grown oat (Avena sativa L.) coleoptiles subjected to either gravitropic or phototropic stimulation and subsequently rotated on a horizontal clinostat. The length measurement was conducted using three 5 mm-long zones delimited by ink markers from the tip. Curvature of each zone was analyzed from the length difference between the two sides. Gravitropism was induced by displacing the seedling from the vertical by 30 degrees or 90 degrees for 25 min. Phototropism was induced by exposing the coleoptile to unilateral blue light for 30 s, which provided a fluence (1.0 micromoles m-2) optimal for the pulse-induced positive phototropism or a lower, suboptimal fluence (0.03 micromoles m-2). After negatively gravitropic bending, the upper two zones straightened rapidly at either displacement angle. After positively phototropic bending, straightening occurred, but only in the top zone and at the lower fluence. The upper two zones straightened rapidly, however, when bilateral blue light (30 s; 15 micromoles m-2 from either direction) was applied 25 min after unilateral stimulation at the higher fluence. Bilateral blue light alone induced no curvature. These results confirm that the straightening of gravitropically bent coleoptiles is autonomic, and suggest that a similar autonomic response participates in the straightening of phototropically bent coleoptiles. Suppression of elongation on the concave side of the coleoptile mainly accounted for gravitropic and phototropic curvatures. The concave side of the top zone shrank during both tropisms. This shrinkage progressed at a high rate from the beginning of curvature response, suggesting that a drop in turgor pressure is the main and direct cause of the shrinkage.

  20. Differential roles of auxin efflux carrier PIN proteins in hypocotyl phototropism of etiolated Arabidopsis seedlings depend on the direction of light stimulus.

    PubMed

    Haga, Ken; Sakai, Tatsuya

    2013-01-01

    In a recent study, we demonstrated that although the auxin efflux carrier PIN-FORMED (PIN) proteins, such as PIN3 and PIN7, are required for the pulse-induced first positive phototropism in etiolated Arabidopsis hypocotyls, they are not necessary for the continuous-light-induced second positive phototropism when the seedlings are grown on the surface of agar medium, which causes the hypocotyls to separate from the agar surface. Previous reports have shown that hypocotyl phototropism is slightly impaired in pin3 single mutants when they are grown along the surface of agar medium, where the hypocotyls always contact the agar, producing some friction. To clarify the possible involvement of PIN3 and PIN7 in continuous-light-induced phototropism, we investigated hypocotyl phototropism in the pin3 pin7 double mutant grown along the surface of agar medium. Intriguingly, the phototropic curvature was slightly impaired in the double mutant when the phototropic stimulus was presented on the adaxial side of the hook, but was not impaired when the phototropic stimulus was presented on the abaxial side of the hook. These results indicate that PIN proteins are required for continuous-light-induced second positive phototropism, depending on the direction of the light stimulus, when the seedlings are in contact with agar medium.

  1. Differential roles of auxin efflux carrier PIN proteins in hypocotyl phototropism of etiolated Arabidopsis seedlings depend on the direction of light stimulus

    PubMed Central

    Haga, Ken; Sakai, Tatsuya

    2013-01-01

    In a recent study, we demonstrated that although the auxin efflux carrier PIN-FORMED (PIN) proteins, such as PIN3 and PIN7, are required for the pulse-induced first positive phototropism in etiolated Arabidopsis hypocotyls, they are not necessary for the continuous-light-induced second positive phototropism when the seedlings are grown on the surface of agar medium, which causes the hypocotyls to separate from the agar surface. Previous reports have shown that hypocotyl phototropism is slightly impaired in pin3 single mutants when they are grown along the surface of agar medium, where the hypocotyls always contact the agar, producing some friction. To clarify the possible involvement of PIN3 and PIN7 in continuous-light-induced phototropism, we investigated hypocotyl phototropism in the pin3 pin7 double mutant grown along the surface of agar medium. Intriguingly, the phototropic curvature was slightly impaired in the double mutant when the phototropic stimulus was presented on the adaxial side of the hook, but was not impaired when the phototropic stimulus was presented on the abaxial side of the hook. These results indicate that PIN proteins are required for continuous-light-induced second positive phototropism, depending on the direction of the light stimulus, when the seedlings are in contact with agar medium. PMID:23104115

  2. GraPhoBox: Gravitropism and phototropism in Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Buizer, K.

    2007-09-01

    The morphology of plants is directed by the directional growth of roots and shoots. Gravity and light direction are the two major environmental stimuli important for directional growth. The 'GraPhoBox' experiment, flown on the Dutch DELTA mission to the ISS in April 2004, tries to elucidate the different effects of gravitropism and phototropism on plants, and their combined effects on plant morphology. Wild-type Arabidopsis thaliana (L.), phototropic-deficient mutants phot1 and gravitropic-deficient mutant pgm1 seeds were germinated in microgravity and in Earth gravity, in low light conditions and darkness. The angle of directional growth of roots and shoots was then assessed. Light is -even in the absense of gravity- the most important environmental cue for directional growth of shoots, while for roots gravity is by far the most important cue, and light is only a very minor factor due to their poor phototropic capacity. Compared to roots, shoots are deviated more than roots in microgravity and therefore less gravity-dependent. All results together suggests that environmental cues are differently percepted by roots and shoots which also adapt differently. Furthermore, environmental cues are probably transferred little or not to the opposite side of the plant.

  3. Phototropic bending of non-elongating and radially growing woody stems results from asymmetrical xylem formation.

    PubMed

    Matsuzaki, Jun; Masumori, Masaya; Tange, Takeshi

    2007-05-01

    Active phototropic bending of non-elongating and radially growing portion of stems (woody stems) has not been previously documented, whereas negative gravitropic bending is well known. We found phototropic bending in woody stems and searched for the underlying mechanism. We inclined 1-year-old Quercus crispula Blume seedlings and unilaterally illuminated them from a horizontal direction perpendicular to ('normal' illumination) or parallel to ('parallel' illumination) the inclination azimuth. With normal illumination, active phototropic bending and xylem formation could be evaluated separately from the negative gravitropic response and vertical deflection resulting from the weight of the seedlings. One-year-old stems with normal illumination bent significantly, with asymmetrical xylem formation towards the illuminated upper surface and side of the stem, whereas those with parallel illumination showed non-significant lateral bending, with asymmetrical xylem formation only on the upper side. A mechanical model was built on the assumption that a bending moment resulted from the asymmetrical xylem formation during phototropic bending of the woody stems. The model fitted the relationship between the observed spatial distributions of the xylem and the observed lateral bending, and thus supported the hypothesis that phototropic bending of woody stems results from asymmetrical xylem formation, as such occurs during gravitropism.

  4. Gravitropism and phototropism of oat coleoptiles: Post-tropic autostraightening and tissue shrinkage during tropism

    NASA Astrophysics Data System (ADS)

    Tarui, Y.; Iino, M.

    1999-01-01

    We measured changes in length on the two opposite sides of the red-light-grown oat (Avena sativa L.) coleoptiles subjected to either gravitropic or phototropic stimulation and subsequently rotated on a horizontal clinostat. The length measurement was conducted using three 5 mm-long zones delimited by ink markers from the tip. Curvature of each zone was analyzed from the length difference between the two sides. Gravitropism was induced by displacing the seedling from the vertical by 30° or 90° for 25 min. Phototropism was induced by exposing the coleoptile to unilateral blue light for 30 s, which provided a fluence (1.0 μmol m-2) optimal for the pulse-induced positive phototropism or a lower, suboptimal fluence (0.03 μmol m-2). After negatively gravitropic bending, the upper two zones straightened rapidly at either displacement angle. After positively phototropic bending, straightening occurred, but only in the top zone and at the lower fluence. The upper two zones straightened rapidly, however, when bilateral blue light (30 s; 15 μmol m-2 from either direction) was applied 25 min after unilateral stimulation at the higher fluence. Bilateral blue light alone induced no curvature. These results confirm that the straightening of gravitropically bent coleoptiles is autonomic, and suggest that a similar autonomic response participates in the straightening of phototropically bent coleoptiles. Suppression of elongation on the concave side of the coleoptile mainly accounted for gravitropic and phototropic curvatures. The concave side of the top zone shrank during both tropisms. This shrinkage progressed at a high rate from the beginning of curvature response, suggesting that a drop in turgor pressure is the main and direct cause of the shrinkage.

  5. Time threshold for second positive phototropism is decreased by a preirradiation with red light

    NASA Technical Reports Server (NTRS)

    Konjevic, R.; Apel, P.; Poff, K. L.

    1992-01-01

    A second positive phototropic response is exhibited by a plant after the time of irradiation has exceeded a time threshold. The time threshold of dark-grown seedlings is about 15 minutes for Arabidopsis thaliana. This threshold is decreased to about 4 minutes by a 669-nanometer preirradiation. Tobacco (Nicotiana tabacum) seedlings show a similar response. The time threshold of dark-grown seedlings is about 60 minutes for tobacco, and is decreased to about 15 minutes after a preirradiation with either 450- or 669- nanometer light. The existence of a time threshold for second positive phototropism and the dependence of this threshold on the irradiation history of the seedling contribute to the complexity of the fluence response relationship for phototropism.

  6. Interaction with gravitropism, reversibility and lateral movements of phototropically stimulated potato shoots.

    PubMed

    Vinterhalter, D; Savić, J; Stanišić, M; Jovanović, Ž; Vinterhalter, B

    2016-07-01

    Phototropic (PT) and gravitropic (GT) bending are the two major tropic movements that determine the spatial position of potato shoots. We studied PT bending of potato plantlets grown under long-day photoperiods in several prearranged position setups providing different interactions with the GT response. Starting with the standard PT stimulation setup composed of unilateral irradiation of vertically positioned shoots, experiments were also done in antagonistic and synergistic setups and in treatments with horizontal displacement of the light source. In the standard setup, PT bending suppressed the GT bending, which could occur only if the PT stimulation was cancelled. The antagonistic position, with phototropism and gravitropism attempting to bend shoots in opposite directions, showed phototropism and gravitropism as independent bending events with the outcome varying throughout the day reflecting diurnal changes in the competence of individual tropic components. Whilst gravitropism was constant, phototropism had a marked daily fluctuation of its magnitude with a prominent morning maximum starting an hour after the dawn in the growth room and lasting for the next 6 h. When phototropism and gravitropism were aligned in a synergistic position, stimulating shoot bending in the same direction, there was little quantitative addition of their individual effects. The long period of morning PT bending maximum enabled multiple PT bending events to be conducted in succession, each one preceded by a separate lag phase. Studies of secondary PT events showed that potato plantlets can follow and adjust their shoot position in response to both vertical and horizontal movements of a light source. PT bending was reversible, since the 180° horizontal change of a blue light (BL) source position resulted in reversal of bending direction after a 20-min-long lag phase.

  7. A common fluence threshold for first positive and second positive phototropism in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Janoudi, A.; Poff, K. L.

    1990-01-01

    The relationship between the amount of light and the amount of response for any photobiological process can be based on the number of incident quanta per unit time (fluence rate-response) or on the number of incident quanta during a given period of irradiation (fluence-response). Fluence-response and fluence rate-response relationships have been measured for second positive phototropism by seedlings of Arabidopsis thaliana. The fluence-response relationships exhibit a single limiting threshold at about 0.01 micromole per square meter when measured at fluence rates from 2.4 x 10(-5) to 6.5 x 10(-3) micromoles per square meter per second. The threshold values in the fluence rate-response curves decrease with increasing time of irradiation, but show a common fluence threshold at about 0.01 micromole per square meter. These thresholds are the same as the threshold of about 0.01 micromole per square meter measured for first positive phototropism. Based on these data, it is suggested that second positive curvature has a threshold in time of about 10 minutes. Moreover, if the times of irradiation exceed the time threshold, there is a single limiting fluence threshold at about 0.01 micromole per square meter. Thus, the limiting fluence threshold for second positive phototropism is the same as the fluence threshold for first positive phototropism. Based on these data, we suggest that this common fluence threshold for first positive and second positive phototropism is set by a single photoreceptor pigment system.

  8. Time threshold for second positive phototropism is decreased by a preirradiation with red light.

    PubMed Central

    Janoudi A-K; Konjevic, R; Apel, P; Poff, K L

    1992-01-01

    A second positive phototropic response is exhibited by a plant after the time of irradiation has exceeded a time threshold. The time threshold of dark-grown seedlings is about 15 minutes for Arabidopsis thaliana. This threshold is decreased to about 4 minutes by a 669-nanometer preirradiation. Tobacco (Nicotiana tabacum) seedlings show a similar response. The time threshold of dark-grown seedlings is about 60 minutes for tobacco, and is decreased to about 15 minutes after a preirradiation with either 450- or 669- nanometer light. The existence of a time threshold for second positive phototropism and the dependence of this threshold on the irradiation history of the seedling contribute to the complexity of the fluence response relationship for phototropism. PMID:11537887

  9. Phototropic leaf movements and photosynthetic performance in an amphibious fern, Marsilea quadrifolia.

    PubMed

    Kao, Wen-Yuan; Lin, Bai-Ling

    2010-09-01

    Diurnal phototropism has not been reported in ferns. In this study we found that the four leaflets of the amphibious fern Marsilea quadrifolia are capable of adjusting their leaflet angle and leaflet azimuth in response to changes in the position of the sun's direct beam, exhibiting more diaphototropic movements (orienting the plane of the lamina perpendicular to incident light) in the morning and late afternoon, and more paraphototropic movements (orienting the plane of the lamina parallel to incident light) at noon. In addition, by cutting off the leaflet lamina and covering portions of leaflets with black tape, the junction between the leaflet and petiole was found to be responsible for light reception. Among the light spectrum investigated, blue light was the most effective at inducing diaphototropism. The role of diurnal phototropism in enhancing carbon return and ameliorating photoinhibition was also evaluated. It was concluded that diurnal phototropic leaf movement represents one of the plastic responses enabling this amphibious fern to grow under terrestrial conditions.

  10. Interaction of gravi- and phototropic stimulation in the response of maize (Zea mays L.) coleoptiles.

    PubMed

    Nick, P; Schafer, E

    1988-02-01

    The influence of gravitropic stimulation upon blue-light-induced first positive phototropism for stimulations in the same (light source and center of gravity opposite to each other) and in opposing directions was investigated in maize coleoptiles by measuring fluence-response patterns. As a result of gravitropic counterstimulation, phototropic bending was transient with maximum curvature occurring 100 min after stimulation. On a horizontal clinostat, however, the seedlings curved for 20 h. Gravistimulation in the opposite direction acted additively upon blue-light curvature. Gravistimulation in the same direction as phototropic stimulation produced a complex behaviour deviating from simple additivity. This pattern can be explained by a gravitropically mediated sensitization of the phototropic reaction, an optimal dependence of differential growth on the sum of photo- and gravistimulation, and blue-light-induced inhibition of gravitropic curvature at high fluences. These findings indicate that several steps of photo- and gravitransduction are separate. Preirradiation with red light desensitized the system independently of applied gravity-treatment, indicating that the site of red-light interaction is common to both transduction chains.

  11. Physical strain-mediated microtubule reorientation in the epidermis of gravitropically or phototropically stimulated maize coleoptiles.

    PubMed

    Fischer, K; Schopfer, P

    1998-07-01

    During gravitropic and phototropic curvature of the maize coleoptile, the cortical microtubules (MTs) adjacent to the outer epidermal cell wall assume opposite orientations at the two sides of the organ. Starting from a uniformly random pattern during straight growth in darkness, the MTs reorientate perpendicularly to the organ axis at the outer (faster growing) side and parallel to the organ axis at the inner (slower growing) side. As similar reorientations can be induced during straight growth by increasing or decreasing the effective auxin concentration, it has been proposed that these reorientations may be used as a diagnostic test for assessing the auxin status of the epidermal cells during tropic curvature. This idea was tested by determining the MT orientations in the coleoptile of intact maize seedlings in which the gravitropic or phototropic curvature was prevented or inversed by an appropriate mechanical counterforce. Forces that just prevented the coleoptile from curving in a gravity or light field prevented reorientations of the MTs. Forces strong enough to overcompensate the tropic stimuli by enforcing curvature in the opposite direction induced reorientations of the MTs opposite to those produced by tropic stimulation. These results show that the MTs at the outer surface of the coleoptile respond to changes in mechanical tissue strain rather than to gravitropic or phototropic stimuli and associated changes at the level of auxin or any other element in the signal transduction chain between perception of tropic stimuli and asymmetric growth response. It is proposed that cortical MTs can act as strain gauges in a positive feed-back regulatory circle utilized for amplification and stabilization of environmentally induced changes in the direction of elongation growth.

  12. Fractional gravity studies on the ISS of sensory mechanisms involved in phototropism

    NASA Astrophysics Data System (ADS)

    Kiss, John Z.; Correll, Melanie; Edelmann, Richard; Millar, Katherine

    The major goals of this research are (1) to better understand cellular mechanisms of pho-totropism in plants and (2) to determine the effects and influence of gravity on light perception in plants. Because of the interfering effect of the strong gravitropic response, microgravity conditions are needed to effectively study phototropism. Experiments performed on the In-ternational Space Station (ISS) were used to explore the mechanisms of both blue-light and red-light-induced phototropism in plants. We utilized the European Modular Cultivation Sys-tem (EMCS), which has environmental controls for plant growth as well as centrifuges for gravity treatments. TROPI-1 (for tropisms) was successfully performed on the ISS during late 2006. We obtained data on seedlings grown in microgravity and discovered a novel positive phototropic response to red light in hypocotyls of seedlings of Arabidopsis thaliana. However, one problem encoun-tered during TROPI-1 was low seed germination due to long storage periods (8 months) in flight hardware. Thus, the originally proposed fractional gravity studies were not performed. TROPI-2 provides an opportunity to regain the results from these important fractional gravity experiments. TROPI-2 experiments will provide a better understanding of how plants integrate sensory input from multiple light and gravity perception systems. This information is important for growing plants on long-term space missions as part of life support systems. The fractional gravity studies contain 0.16g (Moon) and 0.38g (Mars) treatments, so information to be obtained is relevant to exploration objectives

  13. What have we learned about phototropism from spaceflight experiments? Novel responses to light discovered during the Seedling Growth project on the ISS.

    NASA Astrophysics Data System (ADS)

    Kiss, John Z.; Edelmann, Richard; Herranz, Raul; Medina, Francisco Javier; Vandenbrink, Joshua

    2016-07-01

    In response to external stimuli, plants exhibit directed growth responses termed tropisms. Phototropism is directed growth of plants in response to light while gravitropism is the tropistic movement of plants in response to gravity. The integration of these tropisms (along with other growth movements) results in the overall growth form of the plant. Utilizing the European Modular Cultivation System (EMCS) on the International Space Station (ISS), we were able to decouple phototropism from the effects of gravitropism. The Seedling Growth (SG-1, 2, 3) series of experiments employed the centrifuge in the EMCS to create fractional/reduced gravity environments (0, 0.3, 0.5, 0.8 and 1g) to help discern the relationship between the phototropic response and gravitropism in seedlings of Arabidopsis thaliana. In SG, seedlings were exposed to continuous red light, continuous blue light, and red-to-blue light cycles at various gravity levels in order to characterize the phototropic response. Image downlinks from the ISS allowed for analysis of growth and curvature measurements under differential light and gravity conditions. Previous results from our space experiments identified a unique red-light-based phototropism in roots and shoots. The most recent results from SG-1 and SG-2 (2015) reveal a novel positive phototropic curvature in roots of seedlings illuminated with blue light under microgravity conditions. In addition, a positive phototropic response of roots and shoots exposed to red light was observed in microgravity, confirming our previous observations. The phototropic response of shoots to blue light appears to be largely unaffected by fractional gravity. In addition to the WT (Landsberg ecotype), phytochrome A and B mutants were utilized to elucidate the role phytochromes play in blue and red light perception and the resulting phototropic responses. Understanding the relationship between phototropic and gravitropic responses is an important first step in being able

  14. A Common Fluence Threshold for First Positive and Second Positive Phototropism in Arabidopsis thaliana1

    PubMed Central

    Janoudi, Abdul; Poff, Kenneth L.

    1990-01-01

    The relationship between the amount of light and the amount of response for any photobiological process can be based on the number of incident quanta per unit time (fluence rate-response) or on the number of incident quanta during a given period of irradiation (fluence-response). Fluence-response and fluence rate-response relationships have been measured for second positive phototropism by seedlings of Arabidopsis thaliana. The fluence-response relationships exhibit a single limiting threshold at about 0.01 micromole per square meter when measured at fluence rates from 2.4 × 10−5 to 6.5 × 10−3 micromoles per square meter per second. The threshold values in the fluence rateresponse curves decrease with increasing time of irradiation, but show a common fluence threshold at about 0.01 micromole per square meter. These thresholds are the same as the threshold of about 0.01 micromole per square meter measured for first positive phototropism. Based on these data, it is suggested that second positive curvature has a threshold in time of about 10 minutes. Moreover, if the times of irradiation exceed the time threshold, there is a single limiting fluence threshold at about 0.01 micromole per square meter. Thus, the limiting fluence threshold for second positive phototropism is the same as the fluence threshold for first positive phototropism. Based on these data, we suggest that this common fluence threshold for first positive and second positive phototropism is set by a single photoreceptor pigment system. PMID:11537470

  15. In vivo super-resolution imaging of transient retinal phototropism evoked by oblique light stimulation.

    PubMed

    Lu, Yiming; Liu, Changgeng; Yao, Xincheng

    2018-05-01

    Rod-dominated transient retinal phototropism (TRP) has been observed in freshly isolated retinas, promising a noninvasive biomarker for objective assessment of retinal physiology. However, in vivo mapping of TRP is challenging due to its subcellular signal magnitude and fast time course. We report here a virtually structured detection-based super-resolution ophthalmoscope to achieve subcellular spatial resolution and millisecond temporal resolution for in vivo imaging of TRP. Spatiotemporal properties of in vivo TRP were characterized corresponding to variable light intensity stimuli, confirming that TRP is tightly correlated with early stages of phototransduction. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  16. Artificial phototropism based on a photo-thermo-responsive hydrogel

    NASA Astrophysics Data System (ADS)

    Gopalakrishna, Hamsini

    Solar energy is leading in renewable energy sources and the aspects surrounding the efforts to harvest light are gaining importance. One such aspect is increasing the light absorption, where heliotropism comes into play. Heliotropism, the ability to track the sun across the sky, can be integrated with solar cells for more efficient photon collection and other optoelectronic systems. Inspired by plants, which optimize incident sunlight in nature, several researchers have made artificial heliotropic and phototropic systems. This project aims to design, synthesize and characterize a material system and evaluate its application in a phototropic system. A gold nanoparticle (Au NP) incorporated poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was synthesized as a photo-thermo-responsive material in our phototropic system. The Au NPs generate heat from the incident via plasmonic resonance to induce a volume phase change of the thermo-responsive hydrogel PNIPAAm. PNIPAAm shrinks or swells at temperature above or below 32°C. Upon irradiation, the Au NP-PNIPAAm micropillar actuates, specifically bending toward the incident light and precisely following the varying incident angle. Swelling ratio tests, bending angle tests with a static incident light and bending tests with varying angles were carried out on hydrogel samples with varying Au NP concentrations. Swelling ratios ranging from 1.45 to 2.9 were recorded for pure hydrogel samples and samples with very low Au NP concentrations. Swelling ratios of 2.41 and 3.37 were calculated for samples with low and high concentrations of Au NPs, respectively. A bending of up to 88° was observed in Au NP-hydrogel pillars with a low Au NP concentration with a 90° incident angle. The light tracking performance was assessed by the slope of the pillar Bending angle (response angle) vs. Incident light angle plot. A slope of 1 indicates ideal tracking with top of the pillar being normal to the incident light, maximizing the photon

  17. Disruption of ROOT PHOTOTROPISM2 gene does not affect phototropin-mediated stomatal opening.

    PubMed

    Tsutsumi, Toshifumi; Takemiya, Atsushi; Harada, Akiko; Shimazaki, Ken-ichiro

    2013-03-01

    Phototropins (phot1 and phot2), blue light-receptor protein kinases in plants, mediate stomatal opening by activating the plasma membrane H(+)-ATPase in guard cells, but the signaling from phototropins to the H(+)-ATPase remains unknown. A recent study concluded that ROOT PHOTOTROPISM2 (RPT2) is involved in the primary step of this process. However, this conclusion is based solely on the determination of stomatal apertures in the epidermis. We investigated the role of RPT2 in blue light-dependent stomatal opening in more detail. We generated double mutants of rpt2 and phototropins (phot1 or phot2) in the Col ecotype background and obtained the typical phenotypes of rpt2 mutants, including the impairment in phototropism. In contrast, neither blue light-dependent H(+) pumping nor blue light-dependent H(+)-ATPase activation in guard cells was affected in the rpt2 mutants of rpt2, phot1 rpt2, and phot2 rpt2. Stomata in these rpt2 mutants opened widely by blue light in both epidermal peels and intact leaves, and no difference in the responses was found between the wild type and the mutants. From these results, we concluded that RPT2 gene disruption does not affect blue light-dependent stomatal opening. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Interactions between gravitropism and phototropism in plants

    NASA Technical Reports Server (NTRS)

    Correll, Melanie J.; Kiss, John Z.

    2002-01-01

    To receive adequate light and nutrients for survival, plants orient stems and stem-like organs toward light and away from the gravity vector and, conversely, orient roots into the soil, away from light toward the direction of gravity. Therefore, both gravity and light can influence the differential growth of plant organs. To add to the complexity of the interactions between gravity and light, each stimulus can enhance or reduce the effectiveness of the other. On earth, the constant presence of gravity makes it difficult to determine whether plant growth and development is influenced by gravity or light alone or the combination of the two stimuli. In the past decade, our understanding of the gravity and light transduction pathways has advanced through the use of mutants in either gravitropic or phototropic responses and the use of innovative techniques that reduce the effects of one stimulus on the other. Thus, both unique and common elements in the transduction pathways of the gravitropic and phototropic responses have been isolated. This article is focused on the interactions between the light- and gravity-transduction pathways and describes methods used to separate the influences of these two environmental stimuli.

  19. Interactions between gravitropism and phototropism in plants.

    PubMed

    Correll, Melanie J; Kiss, John Z

    2002-06-01

    To receive adequate light and nutrients for survival, plants orient stems and stem-like organs toward light and away from the gravity vector and, conversely, orient roots into the soil, away from light toward the direction of gravity. Therefore, both gravity and light can influence the differential growth of plant organs. To add to the complexity of the interactions between gravity and light, each stimulus can enhance or reduce the effectiveness of the other. On earth, the constant presence of gravity makes it difficult to determine whether plant growth and development is influenced by gravity or light alone or the combination of the two stimuli. In the past decade, our understanding of the gravity and light transduction pathways has advanced through the use of mutants in either gravitropic or phototropic responses and the use of innovative techniques that reduce the effects of one stimulus on the other. Thus, both unique and common elements in the transduction pathways of the gravitropic and phototropic responses have been isolated. This article is focused on the interactions between the light- and gravity-transduction pathways and describes methods used to separate the influences of these two environmental stimuli.

  20. Characterization of adaptation in phototropism of Arabidopsis thaliana

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Janoudi, A.K.; Poff, K.L.

    1991-02-01

    Phototropic curvature has been measured for etiolated Arabidopsis thaliana seedlings with and without a preirradiation. A bilateral preirradiation with 450-nm light at a fluence greater than about 0.1 micromole per square meter causes a rapid densensitization to a subsequent 450-nanometer unilateral irradiation at 0.5 micromole per square meter. Following a refractory period, the capacity to respond phototropically recovers to the predesensitization level, and the response is then enhanced. The length of the refractory period is between 10 and 20 minutes. Both the time needed for recovery and the extent of enhancement increase with increasing fluence of the bilateral preirradiation. Basedmore » on the relative spectral sensitivities of desensitization and enhancement, these responses can be separated. Desensitization is induced by blue light but not by red light. Enhancement, however, is induced by both blue and red light. Thus, enhancement can be induced without desensitization but only vice versa. Both desensitization and enhancement affect only the magnitude of the response and do not affect the fluence threshold.« less

  1. Characterization of adaptation in phototropism of Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Poff, K. L.

    1991-01-01

    Phototropic curvature has been measured for etiolated Arabidopsis thaliana seedlings with and without a preirradiation. A bilateral preirradiation with 450-nm light at a fluence greater than about 0.1 micromole per square meter causes a rapid desensitization to a subsequent 450-nanometer unilateral irradiation at 0.5 micromole per square meter. Following a refractory period, the capacity to respond phototropically recovers to the predesensitization level, and the response is then enhanced. The length of the refractory period is between 10 and 20 minutes. Both the time needed for recovery and the extent of enhancement increase with increasing fluence of the bilateral preirradiation. Based on the relative spectral sensitivities of desensitization and enhancement, these responses can be separated. Desensitization is induced by blue light but not by red light. Enhancement, however, is induced by both blue and red light. Thus, enhancement can be induced without desensitization but not vice versa. Both desensitization and enhancement affect only the magnitude of the response and do not affect the fluence threshold.

  2. Light-Mediated Hormonal Regulation of Plant Growth and Development.

    PubMed

    de Wit, Mieke; Galvão, Vinicius Costa; Fankhauser, Christian

    2016-04-29

    Light is crucial for plant life, and perception of the light environment dictates plant growth, morphology, and developmental changes. Such adjustments in growth and development in response to light conditions are often established through changes in hormone levels and signaling. This review discusses examples of light-regulated processes throughout a plant's life cycle for which it is known how light signals lead to hormonal regulation. Light acts as an important developmental switch in germination, photomorphogenesis, and transition to flowering, and light cues are essential to ensure light capture through architectural changes during phototropism and the shade avoidance response. In describing well-established links between light perception and hormonal changes, we aim to give insight into the mechanisms that enable plants to thrive in variable light environments.

  3. Primary inhibition of hypocotyl growth and phototropism depend differently on phototropin-mediated increases in cytoplasmic calcium induced by blue light.

    PubMed

    Folta, Kevin M; Lieg, Erin J; Durham, Tessa; Spalding, Edgar P

    2003-12-01

    The phototropin photoreceptors transduce blue-light signals into several physiological and developmental responses in plants. A transient rise in cytoplasmic calcium (Ca2+) that begins within seconds of phototropin 1 (phot1) excitation is believed to be an important element in the transduction pathways leading to one or more of the phot1-dependent responses. The goal of the present work was to determine whether the Ca2+ response was necessary for (a). the inhibition of hypocotyl elongation that develops within minutes of the irradiation, and (b). hypocotyl phototropism (curved growth of the stem in response to asymmetric illumination). After determining that pulses of light delivering photon fluences of between 1 and 1000 micromol m-2 induced growth inhibition mediated by phot1 without significant interference from other photosensory pathways, the effect of blocking the Ca2+ rise was assessed. Treatment of seedlings with a Ca2+ chelator prevented the rise in cytoplasmic Ca2+ and prevented phot1-mediated growth inhibition. However, the same chelator treatment did not impair phot1-mediated phototropism. Thus, it appears that the early, transient rise in cytoplasmic Ca2+ is an important intermediary process in at least one but not all phot1-signaling pathways.

  4. Stem phototropism of trees: a possible significant factor in determining stem inclination on forest slopes.

    PubMed

    Matsuzaki, Jun; Masumori, Masaya; Tange, Takeshi

    2006-09-01

    The main stems of trees on forest slopes incline down the slope to various extents that are characteristic of the species. The inclination has been explained as an active response to a horizontally asymmetrical light environment, but the contributing physiological mechanisms are unknown. The present study tested the hypothesis that stem phototropism, gravitropism, or a combination of the two determines the inclination of tree stems on forest slopes. Cryptomeria japonica, Pinus densiflora, Quercus myrsinaefolia and Q. serrata were studied. Measurements were made of stem inclination of mature trees on forest slopes in uniform plantations of each species, and changes in stem inclination of potted seedlings in response to illumination treatments (unilateral or overhead) and inclination treatments (artificially inclined or erect). Indices of phototropic and gravitropic responsiveness were evaluated for each species, calculated from the change in stem inclination in response to artificial inclination with unilateral or overhead illumination. Stem inclination on forest slopes varied significantly among species: Q. serrata inclined most in the down-slope direction, C. japonica inclined the least, and P. densiflora and Q. myrsinaefolia were intermediate. The change in stem inclination of seedlings in each treatment varied significantly among species. One-year-old stems of Q. serrata and 2-year-old stems of Q. myrsinaefolia bent toward the light source. Interspecific variation in the change in stem inclination in response to the unilateral illumination or that in the index of phototropic responsiveness was strongly correlated with the variation in stem inclination on forest slopes. The orientation of woody stems that have finished elongation can be actively controlled by phototropism. Interspecific variation in phototropic responsiveness of trees is a possible significant determinant of interspecific variation in stem inclination on forest slopes.

  5. Stem Phototropism of Trees: A Possible Significant Factor in Determining Stem Inclination on Forest Slopes

    PubMed Central

    MATSUZAKI, JUN; MASUMORI, MASAYA; TANGE, TAKESHI

    2006-01-01

    • Background and Aims The main stems of trees on forest slopes incline down the slope to various extents that are characteristic of the species. The inclination has been explained as an active response to a horizontally asymmetrical light environment, but the contributing physiological mechanisms are unknown. The present study tested the hypothesis that stem phototropism, gravitropism, or a combination of the two determines the inclination of tree stems on forest slopes. • Methods Cryptomeria japonica, Pinus densiflora, Quercus myrsinaefolia and Q. serrata were studied. Measurements were made of stem inclination of mature trees on forest slopes in uniform plantations of each species, and changes in stem inclination of potted seedlings in response to illumination treatments (unilateral or overhead) and inclination treatments (artificially inclined or erect). Indices of phototropic and gravitropic responsiveness were evaluated for each species, calculated from the change in stem inclination in response to artificial inclination with unilateral or overhead illumination. • Key Results Stem inclination on forest slopes varied significantly among species: Q. serrata inclined most in the down-slope direction, C. japonica inclined the least, and P. densiflora and Q. myrsinaefolia were intermediate. The change in stem inclination of seedlings in each treatment varied significantly among species. One-year-old stems of Q. serrata and 2-year-old stems of Q. myrsinaefolia bent toward the light source. Interspecific variation in the change in stem inclination in response to the unilateral illumination or that in the index of phototropic responsiveness was strongly correlated with the variation in stem inclination on forest slopes. • Conclusions The orientation of woody stems that have finished elongation can be actively controlled by phototropism. Interspecific variation in phototropic responsiveness of trees is a possible significant determinant of interspecific

  6. Primary Inhibition of Hypocotyl Growth and Phototropism Depend Differently on Phototropin-Mediated Increases in Cytoplasmic Calcium Induced by Blue Light1

    PubMed Central

    Folta, Kevin M.; Lieg, Erin J.; Durham, Tessa; Spalding, Edgar P.

    2003-01-01

    The phototropin photoreceptors transduce blue-light signals into several physiological and developmental responses in plants. A transient rise in cytoplasmic calcium (Ca2+) that begins within seconds of phototropin 1 (phot1) excitation is believed to be an important element in the transduction pathways leading to one or more of the phot1-dependent responses. The goal of the present work was to determine whether the Ca2+ response was necessary for (a) the inhibition of hypocotyl elongation that develops within minutes of the irradiation, and (b) hypocotyl phototropism (curved growth of the stem in response to asymmetric illumination). After determining that pulses of light delivering photon fluences of between 1 and 1,000 μmol m-2 induced growth inhibition mediated by phot1 without significant interference from other photosensory pathways, the effect of blocking the Ca2+ rise was assessed. Treatment of seedlings with a Ca2+ chelator prevented the rise in cytoplasmic Ca2+ and prevented phot1-mediated growth inhibition. However, the same chelator treatment did not impair phot1-mediated phototropism. Thus, it appears that the early, transient rise in cytoplasmic Ca2+ is an important intermediary process in at least one but not all phot1-signaling pathways. PMID:14645723

  7. BLEACHING MECHANISM OF ORGANIC PHOTOTROPIC SUBSTANCES USED IN RUBY LASERS AS SWITCHES,

    DTIC Science & Technology

    The bleaching process of organic phototropic switches under the effect of ruby laser emission was examined. The effect of the atomic constants of solutions on the bleaching process is evaluated. (Author)

  8. The Enhancement of Phototropin-Induced Phototropic Curvature in Arabidopsis Occurs via a Photoreversible Phytochrome A-Dependent Modulation of Auxin Responsiveness1

    PubMed Central

    Stowe-Evans, Emily L.; Luesse, Darron R.; Liscum, Emmanuel

    2001-01-01

    The induction of phototropism in etiolated (dark-grown) seedlings exposed to an unidirectional pulse or extended irradiation with low fluence rate blue light (BL) requires the action of the phototropin (nph1) BL receptor. Although cryptochromes and phytochromes are not required for phototropic induction, these photoreceptors do modulate the magnitude of curvature resulting from phototropin activation. Modulatory increases in the magnitude of phototropic curvature have been termed “enhancement.” Here, we show that phototropic enhancement is primarily a phytochrome A (phyA)-dependent red/far-red-reversible low fluence response. This phyA-dependent response is genetically separable from the basal phototropin-dependent response, as demonstrated by its retention under extended irradiation conditions in the nph4 mutant background, which normally lacks the basal BL-induced response. It is interesting that the nph4 mutants fail to exhibit the basal phototropin-dependent and phyA-dependent enhancement responses under limiting light conditions. Given that NPH4 encodes a transcriptional activator, auxin response factor 7 (ARF7), we hypothesize that the ultimate target(s) of phyA action during the phototropic enhancement response is a rate-limiting ARF-containing transcriptional complex in which the constituent ARFs can vary in identity or activity depending upon the irradiation condition. PMID:11402210

  9. Role of the Cotyledons in the Phototropic Response of Lavatera cretica Seedlings.

    PubMed

    Schwartz, A; Koller, D

    1980-07-01

    Young seedlings of Lavatera cretica L. exhibit positive phototropism. The hypocotyl perceives unilateral illumination with blue light and curves towards the light source by unequal growth. In addition, the cotyledonary laminas perceive the vectorial component of unilateral illumination with blue light and reorient normal to the beam by creating a turgor differential in their pulvini. Excision of one cotyledon resulted in negative organotropic curvature of the hypocotyl, away from the remaining cotyledon. Illumination of the cotyledonary lamina did not participate in the phototropic curvature of the hypocotyl, so long as the lamina was free to reorient to face the beam. When the lamina was continuously exposed to vectorial photoexcitation, elongation of the hypocotyl on the side carrying the cotyledon could be enhanced, or inhibited, depending on the direction of the beam striking its lamina.

  10. Development of experiments on the interaction between gravitropism and phototropism in Arabidopsis for spaceflight studies

    NASA Astrophysics Data System (ADS)

    Kiss, J. Z.; Kumar, P.; Molas, M. L.; Correll, M. J.; Bowman, R. N.; Eodice, M. T.; Edelmann, R. E.

    The interaction among tropisms is important in determining the final growth form of a plant We have defined and developed a project to study the interaction between gravitropism and phototropism in plants to be performed in microgravity on the International Space Station Specifically we are interested in the role of phytochromes in modulating tropisms in seedlings of Arabidopsis thaliana This project termed TROPI for tropisms is to be performed on the European Modular Cultivation System EMCS which provides an incubator lighting system and high resolution video that are on a centrifuge platform and the experiments will be performed at mu g 1g control and fractional g-levels In order to optimize these spaceflight experiments we have continued ground-based technical tests as well as basic science experiments Long term storage studies of seeds in the TROPI experimental unique equipment EUE were performed and addition of carbon filters to the EUE improved seed germination and seedling growth Since micoarray analyses will be conducted with frozen plant material once samples are returned to earth we performed gene profiling studies using microarrays and quantitative real-time PCR to characterize gene expression changes in roots of seedlings exposed to red light Several genes in signaling pathways acting downstream of phytochromes in red light signaling were identified in roots In addition our results suggest that red and blue light pathways interact in roots and that many elements involved in regulating the responses to

  11. Irradiance-dependent regulation of gravitropism by red light in protonemata of the moss Ceratodon purpureus

    NASA Technical Reports Server (NTRS)

    Kern, V. D.; Sack, F. D.

    1999-01-01

    Apical cells of protonemata of the moss Ceratodon purpureus (Hedw.) Brid. are negatively gravitropic in the dark and positively phototropic in red light. Various fluence rates of unilateral red light were tested to determine whether both tropisms operate simultaneously. At irradiances > or = 140 nmol m-2 s-1 no gravitropism could be detected and phototropism predominated, despite the presence of amyloplast sedimentation. Gravitropism occurred at irradiances lower than 140 nmol m-1 s-1 with most cells oriented above the horizontal but not upright. At these low fluence rates, phototropism was indistinct at 1 g but apparent in microgravity, indicating that gravitropism and phototropism compete at 1 g. The frequency of protonemata that were negatively phototropic varied with the fluence rate and the duration of illumination, as well as with the position of the apical cell before illumination. These data show that the fluence rate of red light regulates whether gravitropism is allowed or completely repressed, and that it influences the polarity of phototropism and the extent to which apical cells are aligned in the light path.

  12. A phytochrome/phototropin chimeric photoreceptor of fern functions as a blue/far-red light-dependent photoreceptor for phototropism in Arabidopsis.

    PubMed

    Kanegae, Takeshi; Kimura, Izumi

    2015-08-01

    In the fern Adiantum capillus-veneris, the phototropic response of the protonemal cells is induced by blue light and partially inhibited by subsequent irradiation with far-red light. This observation strongly suggests the existence of a phytochrome that mediates this blue/far-red reversible response; however, the phytochrome responsible for this response has not been identified. PHY3/NEO1, one of the three phytochrome genes identified in Adiantum, encodes a chimeric photoreceptor composed of both a phytochrome and a phototropin domain. It was demonstrated that phy3 mediates the red light-dependent phototropic response of Adiantum, and that phy3 potentially functions as a phototropin. These findings suggest that phy3 is the phytochrome that mediates the blue/far-red response in Adiantum protonemata. In the present study, we expressed Adiantum phy3 in a phot1 phot2 phototropin-deficient Arabidopsis line, and investigated the ability of phy3 to induce phototropic responses under various light conditions. Blue light irradiation clearly induced a phototropic response in the phy3-expressing transgenic seedlings, and this effect was fully inhibited by simultaneous irradiation with far-red light. In addition, experiments using amino acid-substituted phy3 indicated that FMN-cysteinyl adduct formation in the light, oxygen, voltage (LOV) domain was not necessary for the induction of blue light-dependent phototropism by phy3. We thus demonstrate that phy3 is the phytochrome that mediates the blue/far-red reversible phototropic response in Adiantum. Furthermore, our results imply that phy3 can function as a phototropin, but that it acts principally as a phytochrome that mediates both the red/far-red and blue/far-red light responses. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  13. Phototropic growth control of nanoscale pattern formation in photoelectrodeposited Se–Te films

    PubMed Central

    Sadtler, Bryce; Burgos, Stanley P.; Batara, Nicolas A.; Beardslee, Joseph A.; Atwater, Harry A.; Lewis, Nathan S.

    2013-01-01

    Photoresponsive materials that adapt their morphologies, growth directions, and growth rates dynamically in response to the local incident electromagnetic field would provide a remarkable route to the synthesis of complex 3D mesostructures via feedback between illumination and the structure that develops under optical excitation. We report the spontaneous development of ordered, nanoscale lamellar patterns in electrodeposited selenium–tellurium (Se–Te) alloy films grown under noncoherent, uniform illumination on unpatterned substrates in an isotropic electrolyte solution. These inorganic nanostructures exhibited phototropic growth in which lamellar stripes grew toward the incident light source, adopted an orientation parallel to the light polarization direction with a period controlled by the illumination wavelength, and showed an increased growth rate with increasing light intensity. Furthermore, the patterns responded dynamically to changes during growth in the polarization, wavelength, and angle of the incident light, enabling the template-free and pattern-free synthesis, on a variety of substrates, of woodpile, spiral, branched, or zigzag structures, along with dynamically directed growth toward a noncoherent, uniform intensity light source. Full-wave electromagnetic simulations in combination with Monte Carlo growth simulations were used to model light–matter interactions in the Se–Te films and produced a model for the morphological evolution of the lamellar structures under phototropic growth conditions. The experiments and simulations are consistent with a phototropic growth mechanism in which the optical near-field intensity profile selects and reinforces the dominant morphological mode in the emergent nanoscale patterns. PMID:24218617

  14. Phototropic growth control of nanoscale pattern formation in photoelectrodeposited Se-Te films.

    PubMed

    Sadtler, Bryce; Burgos, Stanley P; Batara, Nicolas A; Beardslee, Joseph A; Atwater, Harry A; Lewis, Nathan S

    2013-12-03

    Photoresponsive materials that adapt their morphologies, growth directions, and growth rates dynamically in response to the local incident electromagnetic field would provide a remarkable route to the synthesis of complex 3D mesostructures via feedback between illumination and the structure that develops under optical excitation. We report the spontaneous development of ordered, nanoscale lamellar patterns in electrodeposited selenium-tellurium (Se-Te) alloy films grown under noncoherent, uniform illumination on unpatterned substrates in an isotropic electrolyte solution. These inorganic nanostructures exhibited phototropic growth in which lamellar stripes grew toward the incident light source, adopted an orientation parallel to the light polarization direction with a period controlled by the illumination wavelength, and showed an increased growth rate with increasing light intensity. Furthermore, the patterns responded dynamically to changes during growth in the polarization, wavelength, and angle of the incident light, enabling the template-free and pattern-free synthesis, on a variety of substrates, of woodpile, spiral, branched, or zigzag structures, along with dynamically directed growth toward a noncoherent, uniform intensity light source. Full-wave electromagnetic simulations in combination with Monte Carlo growth simulations were used to model light-matter interactions in the Se-Te films and produced a model for the morphological evolution of the lamellar structures under phototropic growth conditions. The experiments and simulations are consistent with a phototropic growth mechanism in which the optical near-field intensity profile selects and reinforces the dominant morphological mode in the emergent nanoscale patterns.

  15. Regulation of Hippo signalling by p38 signalling

    PubMed Central

    Huang, Dashun; Li, Xiaojiao; Sun, Li; Huang, Ping; Ying, Hao; Wang, Hui; Wu, Jiarui; Song, Haiyun

    2016-01-01

    The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we identify the p38 mitogen-activated protein kinase (MAPK) pathway as a new upstream branch of the Hippo pathway. In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression. Loss-of-function studies show that lic regulates Hippo signalling in ovary follicle cells and in the wing disc. Epistasis analysis indicates that Mekk1 and lic affect Hippo signalling via p38b and wts. We further demonstrate that the Mekk1-Lic-p38b cascade inhibits Hippo signalling by promoting F-actin accumulation and Jub phosphorylation. In addition, p38 signalling modulates actin filaments and Hippo signalling in parallel to small GTPases Ras, Rac1, and Rho1. Lastly, we show that p38 signalling regulates Hippo signalling in mammalian cell lines. The Lic homologue MKK3 promotes nuclear localization of YAP via the actin cytoskeleton. Upregulation or downregulation of the p38 pathway regulates YAP-mediated transcription. Our work thus reveals a conserved crosstalk between the p38 MAPK pathway and the Hippo pathway in growth regulation. PMID:27402810

  16. Regulation of Hippo signalling by p38 signalling.

    PubMed

    Huang, Dashun; Li, Xiaojiao; Sun, Li; Huang, Ping; Ying, Hao; Wang, Hui; Wu, Jiarui; Song, Haiyun

    2016-08-01

    The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we identify the p38 mitogen-activated protein kinase (MAPK) pathway as a new upstream branch of the Hippo pathway. In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression. Loss-of-function studies show that lic regulates Hippo signalling in ovary follicle cells and in the wing disc. Epistasis analysis indicates that Mekk1 and lic affect Hippo signalling via p38b and wts We further demonstrate that the Mekk1-Lic-p38b cascade inhibits Hippo signalling by promoting F-actin accumulation and Jub phosphorylation. In addition, p38 signalling modulates actin filaments and Hippo signalling in parallel to small GTPases Ras, Rac1, and Rho1. Lastly, we show that p38 signalling regulates Hippo signalling in mammalian cell lines. The Lic homologue MKK3 promotes nuclear localization of YAP via the actin cytoskeleton. Upregulation or downregulation of the p38 pathway regulates YAP-mediated transcription. Our work thus reveals a conserved crosstalk between the p38 MAPK pathway and the Hippo pathway in growth regulation. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  17. Repetition of the classical Boysen-Jensen and Nielsen's experiment on phototropism of oat coleoptiles.

    PubMed

    Yamada, K; Nakano, H; Yokotani-Tomita, K; Bruinsma, J; Yamamura, S; Hasegawa, K

    2000-03-01

    The classical experiment of phototropic response as reported by Boysen-Jensen and Nielsen (1926), which supports the Cholodny-Went theory, was repeated in detail. In the original experiment, etiolated oat (Avena sativa L. cv. Victory) coleoptiles with mica inserted into their tip only showed a positive response when the mica was placed parallel toward the light source and not if it was inserted perpendicularly. On the contrary, we found a positive response irrespective of whether the mica was inserted parallel or perpendicularly to the light source. Damage owing to rude splitting severely reduced the response upon perpendicular insertion. These results invalidate the Boysen-Jensen and Nielsen's experiment as a support of the Cholodny-Went theory and lend support to the Bruinsma-Hasegawa theory ascribing phototropism to the local light-induced accumulation of growth inhibitors against a background of even auxin distribution, the diffusion of auxin being unaffected.

  18. PHOTOTROPIC CIRCUS MOVEMENTS OF LIMAX AS AFFECTED BY TEMPERATURE.

    PubMed

    Crozier, W J; Federighi, H

    1924-09-20

    1. The theory of animal phototropism requires for particular instances a knowledge of the action of light as exerted through each of two bilaterally located receptors functioning singly. The measurement of "circus movements" which this involves must be concerned with such aspects of the reaction as are demonstrably dependent upon the effect of light. 2. The negatively phototropic slug Limax maximus exhibits very definite and continuous circus movement under vertical illumination when one eye-tentacle has been removed. The amplitude of the circling movement, measured in degrees deflection per cm. of path as an index of maintained differential tonus, is intimately related to the concurrent velocity of creeping. Analysis of the orienting mechanism is facilitated by the fact that in gasteropods such as Limax the animal creeps by means of the pedal organ, but orients (turns) by a totally distinct set of muscles in the dorsal and lateral regions of the body wall. 3. The expression of the phototropic orienting tendency, with illumination constant, is greatly influenced by the temperature. Above a zone centering at 15 degrees , the amplitude of turning (degrees per cm. of path) is determined by the temperature in accurate agreement with Arrhenius' equation for chemical reaction velocity, with the critical increment micro = 16,820; and the rate of creeping is progressively less as the temperature rises, micro for its reciprocal being 10,900. Below 15 degrees , the velocity of creeping becomes less the the lower the temperature, micro being again 16,800; while the amplitude of orientation is limited merely by the velocity of creeping, its reciprocal being directly proportional thereto. 4. Measurements of Limax circus movements in terms of turning deflection as function of light intensity must therefore be carried out at a temperature well above 15 degrees . 5. The analysis provides a gross physical model of how an end-result may be influenced by temperature according to the

  19. Modulation of phototropic responsiveness in Arabidopsis through ubiquitination of phototropin 1 by the CUL3-Ring E3 ubiquitin ligase CRL3(NPH3).

    PubMed

    Roberts, Diana; Pedmale, Ullas V; Morrow, Johanna; Sachdev, Shrikesh; Lechner, Esther; Tang, Xiaobo; Zheng, Ning; Hannink, Mark; Genschik, Pascal; Liscum, Emmanuel

    2011-10-01

    Plant phototropism is an adaptive response to changes in light direction, quantity, and quality that results in optimization of photosynthetic light harvesting, as well as water and nutrient acquisition. Though several components of the phototropic signal response pathway have been identified in recent years, including the blue light (BL) receptors phototropin1 (phot1) and phot2, much remains unknown. Here, we show that the phot1-interacting protein NONPHOTOTROPIC HYPOCOTYL3 (NPH3) functions as a substrate adapter in a CULLIN3-based E3 ubiquitin ligase, CRL3(NPH3). Under low-intensity BL, CRL3(NPH3) mediates the mono/multiubiquitination of phot1, likely marking it for clathrin-dependent internalization from the plasma membrane. In high-intensity BL, phot1 is both mono/multi- and polyubiquitinated by CRL3(NPH3), with the latter event targeting phot1 for 26S proteasome-mediated degradation. Polyubiquitination and subsequent degradation of phot1 under high-intensity BL likely represent means of receptor desensitization, while mono/multiubiquitination-stimulated internalization of phot1 may be coupled to BL-induced relocalization of hormone (auxin) transporters.

  20. Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

    PubMed Central

    Norris, Megan L; Pauli, Andrea; Gagnon, James A; Lord, Nathan D; Rogers, Katherine W; Mosimann, Christian; Zon, Leonard I

    2017-01-01

    Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The ‘specification model’ postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the ‘migration model’ posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration. Mesodermal cell migration defects in toddler mutants result from a decrease in animal pole-directed migration and are independent of endoderm. Conversely, endodermal cell migration defects are dependent on a Cxcr4a-regulated tether of the endoderm to mesoderm. These results suggest that Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling and indirectly affects endodermal cell migration via Cxcr4a-signaling. PMID:29117894

  1. Gravitropism and phototropism in protonemata of the moss Pohlia nutans (HEDW.) lindb.

    NASA Astrophysics Data System (ADS)

    Demkiv, O. T.; Kordyum, E. L.; Kardash, O. R.; Khorkavtsiv, O. Ya.

    1999-01-01

    The gravitropism of protonemata of Pohlia nutans is described and compared with that of other mosses. In darkness, protonemata showed negative gravitropism. Under uniform illumination they grew radially over the substrate surface, whereas unilateral illumination induced positive phototropic growth. Gravitropism was coupled with starch synthesis and amyloplast formation. Protonematal gravitropic growth is more variable than the strict negative gravitropism of Ceratodon chloronema.

  2. Modulation of Phototropic Responsiveness in Arabidopsis through Ubiquitination of Phototropin 1 by the CUL3-Ring E3 Ubiquitin Ligase CRL3NPH3[W

    PubMed Central

    Roberts, Diana; Pedmale, Ullas V.; Morrow, Johanna; Sachdev, Shrikesh; Lechner, Esther; Tang, Xiaobo; Zheng, Ning; Hannink, Mark; Genschik, Pascal; Liscum, Emmanuel

    2011-01-01

    Plant phototropism is an adaptive response to changes in light direction, quantity, and quality that results in optimization of photosynthetic light harvesting, as well as water and nutrient acquisition. Though several components of the phototropic signal response pathway have been identified in recent years, including the blue light (BL) receptors phototropin1 (phot1) and phot2, much remains unknown. Here, we show that the phot1-interacting protein NONPHOTOTROPIC HYPOCOTYL3 (NPH3) functions as a substrate adapter in a CULLIN3-based E3 ubiquitin ligase, CRL3NPH3. Under low-intensity BL, CRL3NPH3 mediates the mono/multiubiquitination of phot1, likely marking it for clathrin-dependent internalization from the plasma membrane. In high-intensity BL, phot1 is both mono/multi- and polyubiquitinated by CRL3NPH3, with the latter event targeting phot1 for 26S proteasome-mediated degradation. Polyubiquitination and subsequent degradation of phot1 under high-intensity BL likely represent means of receptor desensitization, while mono/multiubiquitination-stimulated internalization of phot1 may be coupled to BL-induced relocalization of hormone (auxin) transporters. PMID:21990941

  3. Study of plant phototropic responses to different LEDs illumination in microgravity

    NASA Astrophysics Data System (ADS)

    Zyablova, Natalya; Berkovich, Yuliy A.; Skripnikov, Alexander; Nikitin, Vladimir

    2012-07-01

    The purpose of the experiment planned for Russian BION-M #1, 2012, biosatellite is research of Physcomitrella patens (Hedw.) B.S.G. phototropic responses to different light stimuli in microgravity. The moss was chosen as small-size higher plant. The experimental design involves five lightproof culture flasks with moss gametophores fixed inside the cylindrical container (diameter 120 mm; height 240 mm). The plants in each flask are illuminated laterally by one of the following LEDs: white, blue (475 nm), red (625 nm), far red (730 nm), infrared (950 nm). The gametophores growth and bending are captured periodically by means of five analogue video cameras and recorder. The programmable command module controls power supply of each camera and each light source, commutation of the cameras and functioning of video recorder. Every 20 minutes the recorder is sequentially connecting to one of the cameras. This results in a clip, containing 5 sets of frames in a row. After landing time-lapse films are automatically created. As a result we will have five time-lapse films covering transformations in each of the five culture flasks. Onground experiments demonstrated that white light induced stronger gametophores phototropic bending as compared to red and blue stimuli. The comparison of time-lapse recordings in the experiments will provide useful information to optimize lighting assemblies for space plant growth facilities.

  4. Phototropic solar tracking in sunflower plants: an integrative perspective

    PubMed Central

    Kutschera, Ulrich; Briggs, Winslow R.

    2016-01-01

    Background One of the best-known plant movements, phototropic solar tracking in sunflower (Helianthus annuus), has not yet been fully characterized. Two questions are still a matter of debate. (1) Is the adaptive significance solely an optimization of photosynthesis via the exposure of the leaves to the sun? (2) Is shade avoidance involved in this process? In this study, these concepts are discussed from a historical perspective and novel insights are provided. Scope and Methods Results from the primary literature on heliotropic growth movements led to the conclusion that these responses cease before anthesis, so that the flowering heads point to the East. Based on observations on 10-week-old plants, the diurnal East–West oscillations of the upper fifth of the growing stem and leaves in relation to the position of the sun (inclusive of nocturnal re-orientation) were documented, and photon fluence rates on the leaf surfaces on clear, cloudy and rainy days were determined. In addition, the light–response curve of net CO2 assimilation was determined on the upper leaves of the same batch of plants, and evidence for the occurrence of shade-avoidance responses in growing sunflower plants is summarized. Conclusions. Only elongating, vegetative sunflower shoots and the upper leaves perform phototropic solar tracking. Photon fluence response and CO2 assimilation measurements cast doubt on the ‘photosynthesis-optimization hypothesis’ as the sole explanation for the evolution of these plant movements. We suggest that the shade-avoidance response, which maximizes light-driven CO2 assimilation, plays a major role in solar tracking populations of competing sunflower plants, and an integrative scheme of these growth movements is provided. PMID:26420201

  5. Flavonols Mediate Root Phototropism and Growth through Regulation of Proliferation-to-Differentiation Transition.

    PubMed

    Silva-Navas, Javier; Moreno-Risueno, Miguel A; Manzano, Concepción; Téllez-Robledo, Bárbara; Navarro-Neila, Sara; Carrasco, Víctor; Pollmann, Stephan; Gallego, F Javier; Del Pozo, Juan C

    2016-06-01

    Roots normally grow in darkness, but they may be exposed to light. After perceiving light, roots bend to escape from light (root light avoidance) and reduce their growth. How root light avoidance responses are regulated is not well understood. Here, we show that illumination induces the accumulation of flavonols in Arabidopsis thaliana roots. During root illumination, flavonols rapidly accumulate at the side closer to light in the transition zone. This accumulation promotes asymmetrical cell elongation and causes differential growth between the two sides, leading to root bending. Furthermore, roots illuminated for a long period of time accumulate high levels of flavonols. This high flavonol content decreases both auxin signaling and PLETHORA gradient as well as superoxide radical content, resulting in reduction of cell proliferation. In addition, cytokinin and hydrogen peroxide, which promote root differentiation, induce flavonol accumulation in the root transition zone. As an outcome of prolonged light exposure and flavonol accumulation, root growth is reduced and a different root developmental zonation is established. Finally, we observed that these differentiation-related pathways are required for root light avoidance. We propose that flavonols function as positional signals, integrating hormonal and reactive oxygen species pathways to regulate root growth direction and rate in response to light. © 2016 American Society of Plant Biologists. All rights reserved.

  6. Flavonols Mediate Root Phototropism and Growth through Regulation of Proliferation-to-Differentiation Transition

    PubMed Central

    Silva-Navas, Javier; Moreno-Risueno, Miguel A.; Manzano, Concepción; Téllez-Robledo, Bárbara; Navarro-Neila, Sara; Carrasco, Víctor; Pollmann, Stephan

    2016-01-01

    Roots normally grow in darkness, but they may be exposed to light. After perceiving light, roots bend to escape from light (root light avoidance) and reduce their growth. How root light avoidance responses are regulated is not well understood. Here, we show that illumination induces the accumulation of flavonols in Arabidopsis thaliana roots. During root illumination, flavonols rapidly accumulate at the side closer to light in the transition zone. This accumulation promotes asymmetrical cell elongation and causes differential growth between the two sides, leading to root bending. Furthermore, roots illuminated for a long period of time accumulate high levels of flavonols. This high flavonol content decreases both auxin signaling and PLETHORA gradient as well as superoxide radical content, resulting in reduction of cell proliferation. In addition, cytokinin and hydrogen peroxide, which promote root differentiation, induce flavonol accumulation in the root transition zone. As an outcome of prolonged light exposure and flavonol accumulation, root growth is reduced and a different root developmental zonation is established. Finally, we observed that these differentiation-related pathways are required for root light avoidance. We propose that flavonols function as positional signals, integrating hormonal and reactive oxygen species pathways to regulate root growth direction and rate in response to light. PMID:26628743

  7. The gene MACCHI-BOU 4/ENHANCER OF PINOID encodes a NPH3-like protein and reveals similarities between organogenesis and phototropism at the molecular level.

    PubMed

    Furutani, Masahiko; Kajiwara, Takahito; Kato, Takehide; Treml, Birgit S; Stockum, Christine; Torres-Ruiz, Ramón A; Tasaka, Masao

    2007-11-01

    Intercellular transport of the phytohormone auxin is a significant factor for plant organogenesis. To investigate molecular mechanisms by which auxin controls organogenesis, we analyzed the macchi-bou 4 (mab4) mutant identified as an enhancer of pinoid (pid). Although mab4 and pid single mutants displayed relatively mild cotyledon phenotypes, pid mab4 double mutants completely lacked cotyledons. We found that MAB4 was identical to ENHANCER OF PINOID (ENP), which has been suggested to control PIN1 polarity in cotyledon primordia. MAB4/ENP encodes a novel protein, which belongs to the NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) family thought to function as a signal transducer in phototropism and control lateral translocation of auxin. MAB4/ENP mRNA was detected in the protodermal cell layer of the embryo and the meristem L1 layer at the site of organ initiation. In the mab4 embryo, the abundance of PIN1:GFP was severely decreased at the plasma membrane in the protodermal cell layer. In addition, subcellular localization analyses indicated that MAB4/ENP resides on a subpopulation of endosomes as well as on unidentified intracellular compartments. These results indicate that MAB4/ENP is involved in polar auxin transport in organogenesis.

  8. The effect of phototropic centers on energy-extraction efficiency in YSGG:Cr,Nd

    NASA Astrophysics Data System (ADS)

    Evstigneev, V. L.; Zharikov, E. V.; Zavartsev, Iu. D.; Nerobov, O. V.; Studenikin, P. A.

    1990-06-01

    The suppression of amplified spontaneous emission and a 1.5-fold increase in energy efficiency were achieved in YSGG:Cr(3+), Nd(3+) laser crystals under the formation of saturable Cr(4+) centers which absorb at a wavelength of 1.06 micron. It is shown that the efficiency of amplifiers and lasers operating in the Q-switched regime can be significantly enhanced by creating phototropic centers in the doped YSGG crystal.

  9. Photoreceptor-mediated bending towards UV-B in Arabidopsis.

    PubMed

    Vandenbussche, Filip; Tilbrook, Kimberley; Fierro, Ana Carolina; Marchal, Kathleen; Poelman, Dirk; Van Der Straeten, Dominique; Ulm, Roman

    2014-06-01

    Plants reorient their growth towards light to optimize photosynthetic light capture--a process known as phototropism. Phototropins are the photoreceptors essential for phototropic growth towards blue and ultraviolet-A (UV-A) light. Here we detail a phototropic response towards UV-B in etiolated Arabidopsis seedlings. We report that early differential growth is mediated by phototropins but clear phototropic bending to UV-B is maintained in phot1 phot2 double mutants. We further show that this phototropin-independent phototropic response to UV-B requires the UV-B photoreceptor UVR8. Broad UV-B-mediated repression of auxin-responsive genes suggests that UVR8 regulates directional bending by affecting auxin signaling. Kinetic analysis shows that UVR8-dependent directional bending occurs later than the phototropin response. We conclude that plants may use the full short-wavelength spectrum of sunlight to efficiently reorient photosynthetic tissue with incoming light. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  10. Phototropic solar tracking in sunflower plants: an integrative perspective.

    PubMed

    Kutschera, Ulrich; Briggs, Winslow R

    2016-01-01

    One of the best-known plant movements, phototropic solar tracking in sunflower (Helianthus annuus), has not yet been fully characterized. Two questions are still a matter of debate. (1) Is the adaptive significance solely an optimization of photosynthesis via the exposure of the leaves to the sun? (2) Is shade avoidance involved in this process? In this study, these concepts are discussed from a historical perspective and novel insights are provided. Results from the primary literature on heliotropic growth movements led to the conclusion that these responses cease before anthesis, so that the flowering heads point to the East. Based on observations on 10-week-old plants, the diurnal East-West oscillations of the upper fifth of the growing stem and leaves in relation to the position of the sun (inclusive of nocturnal re-orientation) were documented, and photon fluence rates on the leaf surfaces on clear, cloudy and rainy days were determined. In addition, the light-response curve of net CO2 assimilation was determined on the upper leaves of the same batch of plants, and evidence for the occurrence of shade-avoidance responses in growing sunflower plants is summarized. Only elongating, vegetative sunflower shoots and the upper leaves perform phototropic solar tracking. Photon fluence response and CO2 assimilation measurements cast doubt on the 'photosynthesis-optimization hypothesis' as the sole explanation for the evolution of these plant movements. We suggest that the shade-avoidance response, which maximizes light-driven CO2 assimilation, plays a major role in solar tracking populations of competing sunflower plants, and an integrative scheme of these growth movements is provided. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Optical Signal Processing for ASW

    DTIC Science & Technology

    1963-05-01

    considered here. In the initial 1. Weissbein, L. , and O’Brien, S. J., "Attenuation of Thermal Radiation with Phototropic Colorants, " Contract DA-129-QM...COORDINATE Fig. A-1 Energy Diagram of Phototropic Mechanisms Included in Category ii can assume that the A--B conversion of a single local system

  12. Expansion of signal transduction pathways in fungi by extensive genome duplication

    PubMed Central

    Corrochano, Luis M.; Kuo, Alan; Marcet-Houben, Marina; Polaino, Silvia; Salamov, Asaf; Villalobos-Escobedo, José M.; Grimwood, Jane; Álvarez, M. Isabel; Avalos, Javier; Bauer, Diane; Benito, Ernesto P.; Benoit, Isabelle; Burger, Gertraud; Camino, Lola P.; Cánovas, David; Cerdá-Olmedo, Enrique; Cheng, Jan-Fang; Domínguez, Angel; Eliáš, Marek; Eslava, Arturo P.; Glaser, Fabian; Gutiérrez, Gabriel; Heitman, Joseph; Henrissat, Bernard; Iturriaga, Enrique A.; Lang, B. Franz; Lavín, José L.; Lee, Soo Chan; Li, Wenjun; Lindquist, Erika; López-García, Sergio; Luque, Eva M.; Marcos, Ana T.; Martin, Joel; McCluskey, Kevin; Medina, Humberto R.; Miralles-Durán, Alejandro; Miyazaki, Atsushi; Muñoz-Torres, Elisa; Oguiza, José A.; Ohm, Robin A.; Orejas, Margarita; Ortiz-Castellanos, Lucila; Pisabarro, Antonio G.; Rodríguez-Romero, Julio; Ruiz-Herrera, José; Ruiz-Vázquez, Rosa; Sanz, Catalina; Schackwitz, Wendy; Shahriari, Mahdi; Shelest, Ekaterina; Silva-Franco, Fátima; Soanes, Darren; Syed, Khajamohiddin; Tagua, Víctor G.; Talbot, Nicholas J.; Thon, Michael R.; Tice, Hope; de Vries, Ronald P.; Wiebenga, Ad; Yadav, Jagjit S.; Braun, Edward L.; Baker, Scott E.; Garre, Victoriano; Schmutz, Jeremy; Horwitz, Benjamin A.; Torres-Martínez, Santiago; Idnurm, Alexander; Herrera-Estrella, Alfredo; Gabaldón, Toni; Grigoriev, Igor V.

    2016-01-01

    Summary Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides, and show that they have been shaped by an extensive genome duplication or, most likely, a whole genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes. PMID:27238284

  13. Understanding phototropism: from Darwin to today.

    PubMed

    Holland, Jennifer J; Roberts, Diana; Liscum, Emmanuel

    2009-01-01

    Few individuals have had the lasting impact on such a breadth of science as Charles Darwin. While his writings about time aboard the HMS Beagle, his study of the Galapagos islands (geology, fauna, and flora), and his theories on evolution are well known, less appreciated are his studies on plant growth responses to a variety of environmental stimuli. In fact, Darwin, together with the help of his botanist son Francis, left us an entire book, 'The power of movements in plants', describing his many, varied, and insightful observations on this topic. Darwin's findings have provided an impetus for an entire field of study, the study of plant tropic responses, or differential growth (curvature) of plant organs in response to directional stimuli. One tropic response that has received a great deal of attention is the phototropic response, or curvature response to directional light. This review summarizes many of the most significant advancements that have been made in our understanding of this response and place these recent findings in the context of Darwin's initial observations.

  14. Wnt signaling regulates pancreatic β cell proliferation

    PubMed Central

    Rulifson, Ingrid C.; Karnik, Satyajit K.; Heiser, Patrick W.; ten Berge, Derk; Chen, Hainan; Gu, Xueying; Taketo, Makoto M.; Nusse, Roel; Hebrok, Matthias; Kim, Seung K.

    2007-01-01

    There is widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet cells. Wnt signaling is an important regulator of organ growth and cell fates, and genes encoding Wnt-signaling factors are expressed in the pancreas. However, it is unclear whether Wnt signaling regulates pancreatic islet proliferation and differentiation. Here we provide evidence that Wnt signaling stimulates islet β cell proliferation. The addition of purified Wnt3a protein to cultured β cells or islets promoted expression of Pitx2, a direct target of Wnt signaling, and Cyclin D2, an essential regulator of β cell cycle progression, and led to increased β cell proliferation in vitro. Conditional pancreatic β cell expression of activated β-catenin, a crucial Wnt signal transduction protein, produced similar phenotypes in vivo, leading to β cell expansion, increased insulin production and serum levels, and enhanced glucose handling. Conditional β cell expression of Axin, a potent negative regulator of Wnt signaling, led to reduced Pitx2 and Cyclin D2 expression by β cells, resulting in reduced neonatal β cell expansion and mass and impaired glucose tolerance. Thus, Wnt signaling is both necessary and sufficient for islet β cell proliferation, and our study provides previously unrecognized evidence of a mechanism governing endocrine pancreas growth and function. PMID:17404238

  15. Role of Hippo signaling in regulating immunity.

    PubMed

    Hong, Lixin; Li, Xun; Zhou, Dawang; Geng, Jing; Chen, Lanfen

    2018-03-22

    The Hippo signaling pathway has been established as a key regulator of organ size control, tumor suppression, and tissue regeneration in multiple organisms. Recently, emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals. In particular, patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome. MST1/2 kinases, the mammalian orthologs of Drosophila Hippo, may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity. In this review, we present and discuss recent findings of cellular mechanisms/functions of Hippo signaling in the innate immunity in Drosophila and in mammals, T cell immunity, as well as the implications of Hippo signaling for tumor immunity.

  16. Modularized Smad-regulated TGFβ signaling pathway.

    PubMed

    Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

    2012-12-01

    The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.

  17. Feedback regulation of TGF-β signaling.

    PubMed

    Yan, Xiaohua; Xiong, Xiangyang; Chen, Ye-Guang

    2018-01-01

    Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes. Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins, which act as transcription factors to regulate gene expression in the nucleus. Although it is relatively simple and straight-forward, this TGF-β/Smad pathway is regulated by various feedback loops at different levels, including the ligand, the receptor, Smads and transcription, and is thus fine-tuned in terms of signaling robustness, duration, specificity, and plasticity. The precise control gives rise to versatile and context-dependent pathophysiological functions. In this review, we firstly give an overview of TGF-β signaling, and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Hypothalamic mTOR signaling regulates food intake.

    PubMed

    Cota, Daniela; Proulx, Karine; Smith, Kathi A Blake; Kozma, Sara C; Thomas, George; Woods, Stephen C; Seeley, Randy J

    2006-05-12

    The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

  19. Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation

    PubMed Central

    Tape, Christopher J.; Ling, Stephanie; Dimitriadi, Maria; McMahon, Kelly M.; Worboys, Jonathan D.; Leong, Hui Sun; Norrie, Ida C.; Miller, Crispin J.; Poulogiannis, George; Lauffenburger, Douglas A.; Jørgensen, Claus

    2016-01-01

    Summary Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRASG12D) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRASG12D signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRASG12D engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRASG12D. Consequently, reciprocal KRASG12D produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRASG12D alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. Video Abstract PMID:27087446

  20. Light-mediated polarization of the PIN3 auxin transporter for the phototropic response in Arabidopsis.

    PubMed

    Ding, Zhaojun; Galván-Ampudia, Carlos S; Demarsy, Emilie; Łangowski, Łukasz; Kleine-Vehn, Jürgen; Fan, Yuanwei; Morita, Miyo T; Tasaka, Masao; Fankhauser, Christian; Offringa, Remko; Friml, Jiří

    2011-04-01

    Phototropism is an adaptation response, through which plants grow towards the light. It involves light perception and asymmetric distribution of the plant hormone auxin. Here we identify a crucial part of the mechanism for phototropism, revealing how light perception initiates auxin redistribution that leads to directional growth. We show that light polarizes the cellular localization of the auxin efflux carrier PIN3 in hypocotyl endodermis cells, resulting in changes in auxin distribution and differential growth. In the dark, high expression and activity of the PINOID (PID) kinase correlates with apolar targeting of PIN3 to all cell sides. Following illumination, light represses PINOID transcription and PIN3 is polarized specifically to the inner cell sides by GNOM ARF GTPase GEF (guanine nucleotide exchange factor)-dependent trafficking. Thus, differential trafficking at the shaded and illuminated hypocotyl side aligns PIN3 polarity with the light direction, and presumably redirects auxin flow towards the shaded side, where auxin promotes growth, causing hypocotyls to bend towards the light. Our results imply that PID phosphorylation-dependent recruitment of PIN proteins into distinct trafficking pathways is a mechanism to polarize auxin fluxes in response to different environmental and endogenous cues. © 2011 Macmillan Publishers Limited. All rights reserved

  1. Phototropic liquid crystal materials containing naphthopyran dopants

    NASA Astrophysics Data System (ADS)

    Rumi, Mariacristina; Cazzell, Seth; Kosa, Tamas; Sukhomlinova, Ludmila; Taheri, Bahman; Bunning, Timothy; White, Timothy

    2015-03-01

    Dopant molecules dispersed in a liquid crystalline material usually affects the order of the system and the transition temperature between various phases. If the dopants undergo photoisomerization between conformers with different shapes, the interactions with the liquid crystal molecules can be different for the material in the dark and during exposure to light of appropriate wavelength. This can be used to achieve isothermal photoinduced phase transitions (phototropism). With proper selection of materials components, both order-to-disorder and disorder-to-order photoinduced transition have been demonstrated. Isothermal order-increasing transitions have been observed recently using naphthopyran derivatives as dopants. We are investigating the changes in order parameter and transition temperature of liquid crystal mixtures containing naphthopyrans and how they are related to exposure conditions and to the concentration and molecular structure of the dopants. We are also studying the nature of the photoinduced phase transitions, and comparing the behavior with that of azobenzene-doped mixtures, in which exposure to light leads to a decrease, instead of an increase, in the order of the system.

  2. Proteolytic degradation of regulator of G protein signaling 2 facilitates temporal regulation of Gq/11 signaling and vascular contraction.

    PubMed

    Kanai, Stanley M; Edwards, Alethia J; Rurik, Joel G; Osei-Owusu, Patrick; Blumer, Kendall J

    2017-11-24

    Regulator of G protein signaling 2 (RGS2) controls signaling by receptors coupled to the G q/11 class heterotrimeric G proteins. RGS2 deficiency causes several phenotypes in mice and occurs in several diseases, including hypertension in which a proteolytically unstable RGS2 mutant has been reported. However, the mechanisms and functions of RGS2 proteolysis remain poorly understood. Here we addressed these questions by identifying degradation signals in RGS2, and studying dynamic regulation of G q/11 -evoked Ca 2+ signaling and vascular contraction. We identified a novel bipartite degradation signal in the N-terminal domain of RGS2. Mutations disrupting this signal blunted proteolytic degradation downstream of E3 ubiquitin ligase binding to RGS2. Analysis of RGS2 mutants proteolyzed at various rates and the effects of proteasome inhibition indicated that proteolytic degradation controls agonist efficacy by setting RGS2 protein expression levels, and affecting the rate at which cells regain agonist responsiveness as synthesis of RGS2 stops. Analyzing contraction of mesenteric resistance arteries supported the biological relevance of this mechanism. Because RGS2 mRNA expression often is strikingly and transiently up-regulated and then down-regulated upon cell stimulation, our findings indicate that proteolytic degradation tightly couples RGS2 transcription, protein levels, and function. Together these mechanisms provide tight temporal control of G q/11 -coupled receptor signaling in the cardiovascular, immune, and nervous systems. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Evidence from Studies with Acifluorfen for Participation of a Flavin-Cytochrome Complex in Blue Light Photoreception for Phototropism of Oat Coleoptiles 12

    PubMed Central

    Leong, Ta-Yan; Briggs, Winslow R.

    1982-01-01

    The diphenyl ether acifluorfen enhances the blue light-induced absorbance change in Triton X100-solubilized crude membrane preparations from etiolated oat (Avena sativa L. cv. Lodi) coleoptiles. Enhancement of the spectral change is correlated with a change in rate of dark reoxidation of a b-type cytochrome. Similar, although smaller, enhancement was obtained with oxyfluorfen, nitrofen, and bifenox. Light-minus-dark difference spectra in the presence and absence of acifluorfen, and the dithionite-reduced-minus oxidized difference spectrum indicate that acifluorfen is acting specifically at a blue light-sensitive cytochrome-flavin complex. Sodium azide, a flavin inhibitor, decreases the light-induced absorbance change significantly, but does not affect the dark reoxidation of the cytochrome. Hence, it is acting on the light reaction, suggesting that the photoreceptor itself is a flavin. Acifluorfen sensitizes phototropism in dark-grown oat seedlings such that the first positive response occurs with blue light fluences as little as one-third of those required to elicit the same response in seedlings grown in the absence of the herbicide. Both this increase in sensitivity to light and the enhancement of the light-induced cytochrome reduction vary with the applied acifluorfen concentration in a similar manner. The herbicide is without effect either on elongation or on the geotropic response of dark-grown oat seedlings, indicating that acifluorfen is acting specifically close to, or at the photoreceptor end of, the stimulus-response chain. It seems likely that the flavin-cytochrome complex serves to transduce the light signal into curvature in phototropism in oats, with the flavin moiety itself serving as the photoreceptor. PMID:16662593

  4. Aldolase positively regulates of the canonical Wnt signaling pathway

    PubMed Central

    2014-01-01

    The Wnt signaling pathway is an evolutionary conserved system, having pivotal roles during animal development. When over-activated, this signaling pathway is involved in cancer initiation and progression. The canonical Wnt pathway regulates the stability of β-catenin primarily by a destruction complex containing a number of different proteins, including Glycogen synthase kinase 3β (GSK-3β) and Axin, that promote proteasomal degradation of β-catenin. As this signaling cascade is modified by various proteins, novel screens aimed at identifying new Wnt signaling regulators were conducted in our laboratory. One of the different genes that were identified as Wnt signaling activators was Aldolase C (ALDOC). Here we report that ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling in a GSK-3β-dependent mechanism, by disrupting the GSK-3β-Axin interaction and targeting Axin to the dishevelled (Dvl)-induced signalosomes that positively regulate the Wnt pathway thus placing the Aldolase proteins as novel Wnt signaling regulators. PMID:24993527

  5. Neuropilins are positive regulators of Hedgehog signal transduction

    PubMed Central

    Hillman, R. Tyler; Feng, Brian Y.; Ni, Jun; Woo, Wei-Meng; Milenkovic, Ljiljana; Hayden Gephart, Melanie G.; Teruel, Mary N.; Oro, Anthony E.; Chen, James K.; Scott, Matthew P.

    2011-01-01

    The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal transduction during mouse development. Using cell lines lacking key Hh pathway components, we show that Nrps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 overexpression increases maximal Hh target gene activation, indicating the existence of a positive feedback circuit. The regulation of Hh signal transduction by Nrps is conserved between mammals and bony fish, as we show that morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and highly penetrant Hh pathway loss-of-function phenotype. These findings enhance our knowledge of Hh pathway regulation and provide evidence for a conserved nexus between Nrps and this important developmental signaling system. PMID:22051878

  6. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish

    PubMed Central

    Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.

    2016-01-01

    The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

  7. Regulation, Signaling, and Physiological Functions of G-Proteins.

    PubMed

    Syrovatkina, Viktoriya; Alegre, Kamela O; Dey, Raja; Huang, Xin-Yun

    2016-09-25

    Heterotrimeric guanine-nucleotide-binding regulatory proteins (G-proteins) mainly relay the information from G-protein-coupled receptors (GPCRs) on the plasma membrane to the inside of cells to regulate various biochemical functions. Depending on the targeted cell types, tissues, and organs, these signals modulate diverse physiological functions. The basic schemes of heterotrimeric G-proteins have been outlined. In this review, we briefly summarize what is known about the regulation, signaling, and physiological functions of G-proteins. We then focus on a few less explored areas such as the regulation of G-proteins by non-GPCRs and the physiological functions of G-proteins that cannot be easily explained by the known G-protein signaling pathways. There are new signaling pathways and physiological functions for G-proteins to be discovered and further interrogated. With the advancements in structural and computational biological techniques, we are closer to having a better understanding of how G-proteins are regulated and of the specificity of G-protein interactions with their regulators. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Redox-dependent regulation of epidermal growth factor receptor signaling.

    PubMed

    Heppner, David E; van der Vliet, Albert

    2016-08-01

    Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs) that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR), a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

    PubMed

    Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K

    2016-06-01

    The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. © 2016. Published by The Company of Biologists Ltd.

  10. Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling

    PubMed Central

    Skorobogata, Olga; Meng, Jassy; Gauthier, Kimberley; Rocheleau, Christian E.

    2016-01-01

    Epidermal growth factor receptor (EGFR) signaling is essential for animal development, and increased signaling underlies many human cancers. Identifying the genes and cellular processes that regulate EGFR signaling in vivo will help to elucidate how this pathway can become inappropriately activated. Caenorhabditis elegans vulva development provides an in vivo model to genetically dissect EGFR signaling. Here we identified a mutation in dhc-1, the heavy chain of the cytoplasmic dynein minus end–directed microtubule motor, in a genetic screen for regulators of EGFR signaling. Despite the many cellular functions of dynein, DHC-1 is a strong negative regulator of EGFR signaling during vulva induction. DHC-1 is required in the signal-receiving cell and genetically functions upstream or in parallel to LET-23 EGFR. LET-23 EGFR accumulates in cytoplasmic foci in dhc-1 mutants, consistent with mammalian cell studies in which dynein is shown to regulate late endosome trafficking of EGFR with the Rab7 GTPase. However, we found different distributions of LET-23 EGFR foci in rab-7 versus dhc-1 mutants, suggesting that dynein functions at an earlier step of LET-23 EGFR trafficking to the lysosome than RAB-7. Our results demonstrate an in vivo role for dynein in limiting LET-23 EGFR signaling via endosomal trafficking. PMID:27654944

  11. Cell Signaling Pathways that Regulate Ag Presentation

    PubMed Central

    Brutkiewicz, Randy R.

    2016-01-01

    Cell signaling pathways regulate much in the life of a cell: from shuttling cargo through intracellular compartments and onto the cell surface, how it should respond to stress, protecting itself from harm (environmental insults or infections), to ultimately, death by apoptosis. These signaling pathways are important for various aspects of the immune response as well. However, not much is known in terms of the participation of cell signaling pathways in Ag presentation--a necessary first step in the activation of innate and adaptive T cells. In this brief review, I will discuss the known signaling molecules (and pathways) that regulate how Ags are presented to T cells and the mechanism(s) if identified. Studies in this area have important implications in vaccine development and new treatment paradigms against infectious diseases, autoimmunity and cancer. PMID:27824592

  12. POSH regulates Hippo signaling through ubiquitin-mediated expanded degradation.

    PubMed

    Ma, Xianjue; Guo, Xiaowei; Richardson, Helena E; Xu, Tian; Xue, Lei

    2018-02-27

    The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in Drosophila POSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes. Furthermore, knockdown of POSH impedes dextran sulfate sodium-induced Yorkie-dependent intestinal stem cell renewal, suggesting a physiological role of POSH in modulating Hippo signaling. Mechanistically, POSH binds to the C-terminal of Ex and is essential for the Crumbs-induced ubiquitination and degradation of Ex. Our findings establish POSH as a crucial regulator that integrates the signal from the cell surface to negatively regulate Ex-mediated Hippo activation in Drosophila .

  13. Redox-regulated growth factor survival signaling.

    PubMed

    Woolley, John F; Corcoran, Aoife; Groeger, Gillian; Landry, William D; Cotter, Thomas G

    2013-11-20

    Once the thought of as unwanted byproducts of cellular respiration in eukaryotes, reactive oxygen species (ROS) have been shown to facilitate essential physiological roles. It is now understood that ROS are critical mediators of intracellular signaling. Control of signal transduction downstream of growth factor receptors by ROS is a complex process whose details are only recently coming to light. Indeed, recent evidence points to control of signal propagation by ROS at multiple levels in the typical cascade. Growth factor stimulation activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) at the membrane, producing superoxide in the extracellular matrix, which is catalyzed to the membrane-permeable hydrogen peroxide (H2O2) that mediates intracellular signaling events. The potential for H2O2, however, to disrupt cellular functions by damaging proteins and nucleic acids demands that its levels are kept in check by receptor-associated peroxiredoxins. This interplay of Nox and peroxiredoxin activity moderates levels of H2O2 sufficiently to modify signaling partners locally. Among the best studied of these partners are redox-controlled phosphatases that are inactivated by H2O2. Phosphatases regulate signal propagation downstream of receptors, and thus their inactivation allows a further level of control. Transmission of information further downstream to targets such as transcription factors, themselves regulated by ROS, completes this pathway. Thus, signal propagation or attenuation can be dictated by ROS at multiple points. Given the complex nature of these processes, we envisage the emerging trends in the field of redox signaling in the context of growth factor stimulation.

  14. NFκB signaling regulates embryonic and adult neurogenesis

    PubMed Central

    ZHANG, Yonggang; HU, Wenhui

    2013-01-01

    Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic and extrinsic factors and complex signaling pathways. Misregulated neurogenesis contributes much to a large range of neurodevelopmental defects and neurodegenerative diseases. The signaling of NFκB regulates many genes important in inflammation, immunity, cell survival and neural plasticity. During neurogenesis, NFκB signaling mediates the effect of numerous niche factors such as cytokines, chemokines, growth factors, extracellular matrix molecules, but also crosstalks with other signaling pathways such as Notch, Shh, Wnt/β-catenin. This review summarizes current progress on the NFκB signaling in all aspects of neurogenesis, focusing on the novel role of NFκB signaling in initiating early neural differentiation of neural stem cells and embryonic stem cells. PMID:24324484

  15. Subpicosecond pulses from a neodymium-glass laser with a solid-liquid phototropic shutter

    NASA Astrophysics Data System (ADS)

    Altshuler, G. B.; Dulneva, E. G.; Karasev, V. B.; Okishev, A. V.; Telegin, L. S.

    1985-02-01

    Subpicosecond, spectrally limited pulses were generated in a mode-locked silicate-Nd-glass laser by means of a phototropic shutter. The shutter featured molecules of an organic dye added to a matrix composed of an isobutyl alcohol-filled quartz micropore glass plate. A coating on the inner surface of one of the cell windows was 0.99 reflective at the lasing wavelength. Single pulses with 0.5-1 psec length were generated, validating the use of a solid-liquid shutter for producing subpicosecond pulses with a Nd-glass laser. Furthermore, the liquid component permitted output powers of up to 5 W/sq cm without eliciting thermooptical effects.

  16. Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

    PubMed

    Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

    2014-01-17

    The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

  17. Regulation of the Hippo signaling pathway by ubiquitin modification.

    PubMed

    Kim, Youngeun; Jho, Eek-Hoon

    2018-03-01

    The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. β-TrCP is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway. [BMB Reports 2018; 51(3): 143-150].

  18. Dynamic Redox Regulation of IL-4 Signaling.

    PubMed

    Dwivedi, Gaurav; Gran, Margaret A; Bagchi, Pritha; Kemp, Melissa L

    2015-11-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation.

  19. Dynamic Redox Regulation of IL-4 Signaling

    PubMed Central

    Dwivedi, Gaurav; Gran, Margaret A.; Bagchi, Pritha; Kemp, Melissa L.

    2015-01-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

  20. Calcium signaling in taste cells: regulation required.

    PubMed

    Medler, Kathryn F

    2010-11-01

    Peripheral taste receptor cells depend on distinct calcium signals to generate appropriate cellular responses that relay taste information to the central nervous system. Some taste cells have conventional chemical synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release from stores to formulate an output signal through a hemichannel. Despite the importance of calcium signaling in taste cells, little is known about how these signals are regulated. This review summarizes recent studies that have identified 2 calcium clearance mechanisms expressed in taste cells, including mitochondrial calcium uptake and sodium/calcium exchangers (NCXs). These studies identified a unique constitutive calcium influx that contributes to maintaining appropriate calcium homeostasis in taste cells and the role of the mitochondria and exchangers in this process. The additional role of NCXs in the regulation of evoked calcium responses is also discussed. Clearly, calcium signaling is a dynamic process in taste cells and appears to be more complex than has previously been appreciated.

  1. Plant Growth/Plant Phototropism - Skylab Student Experiment ED-61/62

    NASA Technical Reports Server (NTRS)

    1973-01-01

    This chart describes the Skylab student experiment ED-61, Plant Growth, and experiment ED-62, Plant Phototropism. Two similar proposals were submitted by Joel G. Wordekemper of West Point, Nebraska, and Donald W. Schlack of Downey, California. Wordekemper's experiment (ED-61) was to see how the lack of gravity would affect the growth of roots and stems of plants. Schlack's experiment (ED-62) was to study the effect of light on a seed developing in zero gravity. The growth container of the rice seeds for their experiment consisted of eight compartments arranged in two parallel rows of four. Each had two windowed surfaces to allow periodic photography of the developing seedlings. In March 1972, NASA and the National Science Teachers Association selected 25 experiment proposals for flight on Skylab. Science advisors from the Marshall Space Flight Center aided and assisted the students in developing the proposals for flight on Skylab.

  2. Signal-activated phospholipase regulation of leukocyte chemotaxis.

    PubMed

    Cathcart, Martha K

    2009-04-01

    Signal-activated phospholipases are a recent focus of the rapidly growing field of lipid signaling. The extent of their impact on the pathways regulating diverse cell functions is beginning to be appreciated. A critical step in inflammation is the attraction of leukocytes to injured or diseased tissue. Chemotaxis of leukocytes, a requisite process for monocyte and neutrophil extravasation from the blood into tissues, is a critical step for initiating and maintaining inflammation in both acute and chronic settings. Recent studies have identified new important and required roles for two signal-activated phospholipases A2 (PLA2) in regulating chemotaxis. The two intracellular phospholipases, cPLA2alpha (Group IVA) and iPLA2beta (Group VIA), act in parallel to provide distinct lipid mediators at different intracellular sites that are both required for leukocytes to migrate toward the chemokine monocyte chemoattractant protein-1. This review will summarize the separate roles of these phospholipases as well as what is currently known about the influence of two other classes of intracellular signal-activated phospholipases, phospholipase C and phospholipase D, in regulating chemotaxis in eukaryotic cells, but particularly in human monocytes. The contributions of these phospholipases to chemotaxis both in vitro and in vivo will be highlighted.

  3. Regulation of Hedgehog Signalling Inside and Outside the Cell

    PubMed Central

    Ramsbottom, Simon A.; Pownall, Mary E.

    2016-01-01

    The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis. Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known to act as a morphogen that diffuses to elicit pattern formation. Heparan sulfate proteoglycans (HSPGs) play a major role in the regulation of Hh distribution outside the cell. Inside the cell, the primary cilium provides an important hub for processing the Hh signal in vertebrates. This review will summarise the current understanding of how the Hh pathway is regulated from ligand production, release, and diffusion, through to signal reception and intracellular transduction. PMID:27547735

  4. Negative regulation of BMP signaling by the ski oncoprotein.

    PubMed

    Luo, Kunxin

    2003-01-01

    The bone morphogenetic proteins (BMPs) play important roles in the regulation of multiple aspects of vertebrate development. BMPs signal through the cell surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. The activity of this signal pathway can be modulated both by extracellular factors that regulate the binding of BMPs to the receptor and by intracellular proteins that interact with the Smad proteins. We have shown that Ski is an important negative regulator of the Smad proteins. Ski can bind to the BMP-Smad protein complexes in response to BMP and repress their ability to activate BMP target genes through disruption of a functional Smad complex and through recruitment of transcriptional co-repressors. The antagonism of BMP signaling by Ski results in neural specification in Xenopus embryos and inhibition of osteoblast differentiation in mouse bone-marrow stromal progenitor cells. This ability to modulate BMP signaling by Ski may play an important role in the regulation of craniofacial, neuronal, and skeletal muscle development.

  5. Dependence of the phototropic response of Arabidopsis thaliana on fluence rate and wavelength

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Konjevic, R.; Steinitz, B.; Poff, K.L.

    1989-12-01

    In the phototropic response of Arabidopsis thaliana seedlings, the shape of the fluence-response relation depends on fluence rate and wavelength. At low fluence rates, the response to 450-nm light is characterized by a single maximum at about 0.3 {mu}mol{center dot}m{sup {minus}2}. At higher fluence rates, the response shows two distinct maxima, I and II, at 0.3 and 3.5 {mu}mol{center dot}m{sup {minus}2}, respectively. The response to 500-nm light shows a single maximum at 2 {mu}mol{center dot}m{sup {minus}2}, and the response to 510-nm light shows a single maximum at 4.5 {mu}mol{center dot}m{sup {minus}2}, independent of fluence rate. The response to 490-nm lightmore » shows a maximal at 4.5 {mu}mol{center dot}m{sup {minus}2} and a shoulder at about 0.6 {mu}mol{center dot}m{sup {minus}2}. Preirradiation with high-fluence 510-nm light from above, immediately followed by unilateral 450-nm light, eliminates maximum II but not maximum I. Preirradiation with high-fluence 450-nm light from above eliminates the response to subsequent unilateral irradiation with either 450-nm or 510-nm light. The recovery of the response following high-fluence 450-nm light is considerably slower than the recovery following high-fluence 510-nm light. Unilateral irradiation with low-fluence 510-nm light followed by 450-nm light results in curvature that is approximately the sum of those produced by either irradiation alone. Based on these results, it is proposed that phototropism in A. thaliana seedlings is mediated by at least two blue-light photoreceptor pigments.« less

  6. The use of microgravity to study phototropism-the TROPI experiments on the ISS

    NASA Astrophysics Data System (ADS)

    Kiss, John Z.; Kumar, Prem; Correll, Melanie; Edelmann, Richard

    On Earth, it is very difficult to study the interacting effects of gravity and other stimuli such as light on plant growth. However, a project termed TROPI (for tropisms) was performed to examine these interactions in seedlings of Arabidopsis thaliana that were grown on the International Space Station (ISS). A major goal of these experiments was to gain insights into the cellular and molecular mechanisms of phototropism, the directed growth of plants in response to light. TROPI utilized the EMCS (European Modular Cultivation System) which has an incubator, lighting, high-resolution video and two centrifuge platforms so that experiments were conducted at µg, 1g (control), and fractional g-levels during ISS Increment 14 from October to December 2006. Dry seeds of the wild type (Landsberg strain) along with the phytochrome mutants phyA, phyB, and phyAB were used in these studies. The experiments were started by the automated hydration of seeds using hardware specially designed for these experiments. The time line consisted of a growth phase and a stimulation phase in which seedlings received unilateral red or blue illumination. At the end of the experiments, an astronaut placed the seedlings in an on-orbit -80° C degree freezer. The data obtained from TROPI consisted of video observations of seedlings and frozen specimens which are being used in microarray studies to monitor gene expression changes in the different light and gravity treatments. Video tapes and frozen samples were returned on three space shuttle missions in 2007, and we are in the process of analyzing the data from both types of experiments. This paper will focus on growth and phototropism of seedlings in response to blue and red light.

  7. Signaling, Gene Regulation and Cancer | Center for Cancer Research

    Cancer.gov

    Although there have been tremendous progress in cancer research and treatment, the mortality caused by this disease is still very high. Cancer is the leading cause of death worldwide and second leading cause of death in the United States of America. Signaling, Gene Regulation and Cancer covers topics including the role of various signaling pathways in development, regulation

  8. Effect of xenon on the excited states of phototropic receptor flavin in corn seedlings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vierstra, R.D.; Poff, K.L.; Walker, E.B.

    1981-05-01

    The chemically inert, water-soluble heavy atom gas, xenon, at millimolar concentrations specifically quenches the triplet excited state of flavin in solution without quenching the flavin singlet excited state. The preferential quenching of the flavin triplet over the singlet excited state by Xe has been established by showing that the flavin triplet-sensitized photooxidation of NADH is inhibited while the fluorescence intensity and lifetime of flavin are not affected by Xe. No significant inhibition of phototropism and geotropism by Xe was observed, suggesting that a flavin singlet state is more likely involved than the triplet state in the primary photoprocess of phototropismmore » in corn.« less

  9. Influence of hook position on phototropic and gravitropic curvature by etiolated hypocotyls of Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Khurana, J. P.; Best, T. R.; Poff, K. L.

    1989-01-01

    Phototropic and gravitropic curvature by hypocotyls of Arabidopsis thaliana is minimal when the side of the hook with the cotyledons attached is positioned toward the direction of tropistic curvature, and maximal when that side of the hook is positioned away from the direction of tropistic curvature. Based on these data, it is proposed that the position of the hook with attached cotyledons affects curvature and not stimulus perception. A randomly oriented population of plants exhibited considerable heterogeneity in tropistic curvature. This heterogeneity arises at least in part from the dependence of curvature on the position of the hook.

  10. Influence of hook position on phototropic and gravitropic curvature by etiolated hypocotyls of Arabidopsis thaliana.

    PubMed

    Khurana, J P; Best, T R; Poff, K L

    1989-01-01

    Phototropic and gravitropic curvature by hypocotyls of Arabidopsis thaliana is minimal when the side of the hook with the cotyledons attached is positioned toward the direction of tropistic curvature, and maximal when that side of the hook is positioned away from the direction of tropistic curvature. Based on these data, it is proposed that the position of the hook with attached cotyledons affects curvature and not stimulus perception. A randomly oriented population of plants exhibited considerable heterogeneity in tropistic curvature. This heterogeneity arises at least in part from the dependence of curvature on the position of the hook.

  11. Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport.

    PubMed

    Jin, Daqing; Ni, Terri T; Sun, Jianjian; Wan, Haiyan; Amack, Jeffrey D; Yu, Guangju; Fleming, Jonathan; Chiang, Chin; Li, Wenyan; Papierniak, Anna; Cheepala, Satish; Conseil, Gwenaëlle; Cole, Susan P C; Zhou, Bin; Drummond, Iain A; Schuetz, John D; Malicki, Jarema; Zhong, Tao P

    2014-09-01

    Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4(T804M) mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis.

  12. Neurotrophin signalling pathways regulating neuronal apoptosis.

    PubMed

    Miller, F D; Kaplan, D R

    2001-07-01

    Recent evidence indicates that naturally occurring neuronal death in mammals is regulated by the interplay between receptor-mediated prosurvival and proapoptotic signals. The neurotrophins, a family of growth factors best known for their positive effects on neuronal biology, have now been shown to mediate both positive and negative survival signals, by signalling through the Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival have been difficult to decipher, largely because both can signal independently or coincidentally, depending upon the cell or developmental context. Nonetheless, the past several years have seen significant advances in our understanding of this receptor signalling system. In this review, we focus on the proapoptotic actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between Trk and p75NTR that determines neuronal survival.

  13. A Pivotal Role of DELLAs in Regulating Multiple Hormone Signals.

    PubMed

    Davière, Jean-Michel; Achard, Patrick

    2016-01-04

    Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey information from multiple developmental and environmental signals. Moreover, in plants many processes such as growth, development, and defense are regulated in similar ways by multiple hormones. Among them, gibberellins (GAs) are phytohormones with pleiotropic actions, regulating various growth processes throughout the plant life cycle. Previous work has revealed extensive interplay between GAs and other hormones, but the molecular mechanism became apparent only recently. Molecular and physiological studies have demonstrated that DELLA proteins, considered as master negative regulators of GA signaling, integrate multiple hormone signaling pathways through physical interactions with transcription factors or regulatory proteins from different families. In this review, we summarize the latest progress in GA signaling and its direct crosstalk with the main phytohormone signaling, emphasizing the multifaceted role of DELLA proteins with key components of major hormone signaling pathways. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  14. Plastids Are Major Regulators of Light Signaling in Arabidopsis1[W][OA

    PubMed Central

    Ruckle, Michael E.; Burgoon, Lyle D.; Lawrence, Lauren A.; Sinkler, Christopher A.; Larkin, Robert M.

    2012-01-01

    We previously provided evidence that plastid signaling regulates the downstream components of a light signaling network and that this signal integration coordinates chloroplast biogenesis with both the light environment and development by regulating gene expression. We tested these ideas by analyzing light- and plastid-regulated transcriptomes in Arabidopsis (Arabidopsis thaliana). We found that the enrichment of Gene Ontology terms in these transcriptomes is consistent with the integration of light and plastid signaling (1) down-regulating photosynthesis and inducing both repair and stress tolerance in dysfunctional chloroplasts and (2) helping coordinate processes such as growth, the circadian rhythm, and stress responses with the degree of chloroplast function. We then tested whether factors that contribute to this signal integration are also regulated by light and plastid signals by characterizing T-DNA insertion alleles of genes that are regulated by light and plastid signaling and that encode proteins that are annotated as contributing to signaling, transcription, or no known function. We found that a high proportion of these mutant alleles induce chloroplast biogenesis during deetiolation. We quantified the expression of four photosynthesis-related genes in seven of these enhanced deetiolation (end) mutants and found that photosynthesis-related gene expression is attenuated. This attenuation is particularly striking for Photosystem II subunit S expression. We conclude that the integration of light and plastid signaling regulates a number of END genes that help optimize chloroplast function and that at least some END genes affect photosynthesis-related gene expression. PMID:22383539

  15. Mechanical Regulation of Signaling Pathways in Bone

    PubMed Central

    Thompson, William R.; Rubin, Clinton T.; Rubin, Janet

    2012-01-01

    A wide range of cell types depend on mechanically induced signals to enable appropriate physiological responses. The skeleton is particularly dependent on mechanical information to guide the resident cell population towards adaptation, maintenance and repair. Research at the organ, tissue, cell and molecular levels has improved our understanding of how the skeleton can recognize the functional environment, and how these challenges are translated into cellular information that can site-specifically alter phenotype. This review first considers those cells within the skeleton that are responsive to mechanical signals, including osteoblasts, osteoclasts, osteocytes and osteoprogenitors. This is discussed in light of a range of experimental approaches that can vary parameters such as strain, fluid shear stress, and pressure. The identity of mechanoreceptor candidates is approached, with consideration of integrins, pericellular tethers, focal adhesions, ion channels, cadherins, connexins, and the plasma membrane including caveolar and non-caveolar lipid rafts and their influence on integral signaling protein interactions. Several mechanically regulated intracellular signaling cascades are detailed including activation of kinases (Akt, MAPK, FAK), β-catenin, GTPases, and calcium signaling events. While the interaction of bone cells with their mechanical environment is complex, an understanding of mechanical regulation of bone signaling is crucial to understanding bone physiology, the etiology of diseases such as osteoporosis, and to the development of interventions to improve bone strength. PMID:22575727

  16. New Insights from Drosophila into the Regulation of EGFR Signaling.

    PubMed

    Harden, Nicholas

    2017-01-01

    Genetic analysis of Egfr signaling in Drosophila has a long-standing track record of making important contributions to our understanding of the Egfr pathway. While the central Ras/MAPK pathway has long been well defined, there is much to learn with regard to its cross talk with other pathways and how it is regulated. A better understanding of the regulation of Egfr signaling is of particular interest with regard to the participation of misregulated Egfr signaling in tumorigenesis. Recent studies in the fly have led to some surprising results, identifying regulators of Egfr acting in unexpected ways.

  17. Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9

    PubMed Central

    Kohn, Anat; Rutkowski, Timothy P; Liu, Zhaoyang; Mirando, Anthony J; Zuscik, Michael J; O’Keefe, Regis J; Hilton, Matthew J

    2015-01-01

    RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissue-specific Rbpjk mutant (Prx1Cre;Rbpjkf/f), Rbpjk mutant/Sox9 haploinsufficient (Prx1Cre;Rbpjkf/f;Sox9f/+), and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors. PMID:26558140

  18. Signaling mechanisms regulating adult neural stem cells and neurogenesis

    PubMed Central

    Faigle, Roland; Song, Hongjun

    2012-01-01

    Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

  19. The R-spondin family of proteins: emerging regulators of WNT signaling

    PubMed Central

    Jin, Yong-Ri; Yoon, Jeong Kyo

    2012-01-01

    Recently, the R-spondin (RSPO) family of proteins has emerged as important regulators of WNT signaling. Considering the wide spectrum of WNT signaling functions in normal biological processes and disease conditions, there has been a significantly growing interest in understanding the functional roles of RSPOs in multiple biological processes and determining the molecular mechanisms by which RSPOs regulate the WNT signaling pathway. Recent advances in the RSPO research field revealed some of the in vivo functions of RSPOs and provided new information regarding the mechanistic roles of RSPO activity in regulation of WNT signaling. Herein, we review recent progress in RSPO research with an emphasis on signaling mechanisms and biological functions. PMID:22982762

  20. Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior

    NASA Technical Reports Server (NTRS)

    Kuhn, H.; Galston, A. W.

    1992-01-01

    Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

  1. Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior.

    PubMed

    Kuhn, H; Galston, A W

    1992-01-01

    Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

  2. Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion.

    PubMed

    Luis, Tiago C; Naber, Brigitta A E; Roozen, Paul P C; Brugman, Martijn H; de Haas, Edwin F E; Ghazvini, Mehrnaz; Fibbe, Willem E; van Dongen, Jacques J M; Fodde, Riccardo; Staal, Frank J T

    2011-10-04

    Canonical Wnt signaling has been implicated in the regulation of hematopoiesis. By employing a Wnt-reporter mouse, we observed that Wnt signaling is differentially activated during hematopoiesis, suggesting an important regulatory role for specific Wnt signaling levels. To investigate whether canonical Wnt signaling regulates hematopoiesis in a dosage-dependent fashion, we analyzed the effect of different mutations in the Adenomatous polyposis coli gene (Apc), a negative modulator of the canonical Wnt pathway. By combining different targeted hypomorphic alleles and a conditional deletion allele of Apc, a gradient of five different Wnt signaling levels was obtained in vivo. We here show that different, lineage-specific Wnt dosages regulate hematopoietic stem cells (HSCs), myeloid precursors, and T lymphoid precursors during hematopoiesis. Differential, lineage-specific optimal Wnt dosages provide a unifying concept that explains the differences reported among inducible gain-of-function approaches, leading to either HSC expansion or depletion of the HSC pool. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Go Signaling in Mushroom Bodies Regulates Sleep in Drosophila

    PubMed Central

    Guo, Fang; Yi, Wei; Zhou, Mingmin; Guo, Aike

    2011-01-01

    Study Objectives: Sleep is a fundamental physiological process and its biological mechanisms are poorly understood. In Drosophila melanogaster, heterotrimeric Go protein is abundantly expressed in the brain. However, its post-developmental function has not been extensively explored. Design: Locomotor activity was measured using the Drosophila Activity Monitoring System under a 12:12 LD cycle. Sleep was defined as periods of 5 min with no recorded activity. Results: Pan-neuronal elevation of Go signaling induced quiescence accompanied by an increased arousal threshold in flies. By screening region-specific GAL4 lines, we mapped the sleep-regulatory function of Go signaling to mushroom bodies (MBs), a central brain region which modulates memory, decision making, and sleep in Drosophila. Up-regulation of Go activity in these neurons consolidated sleep while inhibition of endogenous Go via expression of Go RNAi or pertussis toxin reduced and fragmented sleep, indicating that the Drosophila sleep requirement is affected by levels of Go activity in the MBs. Genetic interaction results showed that Go signaling serves as a neuronal transmission inhibitor in a cAMP-independent pathway. Conclusion: Go signaling is a novel signaling pathway in MBs that regulates sleep in Drosophila. Citation: Guo F; Yi W; Zhou M; Guo A. Go signaling in mushroom bodies regulates sleep in drosophila. SLEEP 2011;34(3):273-281. PMID:21358844

  4. Regulators and effectors of bone morphogenetic protein signalling in the cardiovascular system.

    PubMed

    Luo, Jiang-Yun; Zhang, Yang; Wang, Li; Huang, Yu

    2015-07-15

    Bone morphogenetic proteins (BMPs) play key roles in the regulation of cell proliferation, differentiation and apoptosis in various tissues and organs, including the cardiovascular system. BMPs signal through both Smad-dependent and -independent cascades to exert a wide spectrum of biological activities. Cardiovascular disorders such as abnormal angiogenesis, atherosclerosis, pulmonary hypertension and cardiac hypertrophy have been linked to aberrant BMP signalling. To correct the dysregulated BMP signalling in cardiovascular pathogenesis, it is essential to get a better understanding of how the regulators and effectors of BMP signalling control cardiovascular function and how the dysregulated BMP signalling contributes to cardiovascular dysfunction. We hence highlight several key regulators of BMP signalling such as extracellular regulators of ligands, mechanical forces, microRNAs and small molecule drugs as well as typical BMP effectors like direct downstream target genes, mitogen-activated protein kinases, reactive oxygen species and microRNAs. The insights into these molecular processes will help target both the regulators and important effectors to reverse BMP-associated cardiovascular pathogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  5. Dancing with Hormones: A Current Perspective of Nitrate Signaling and Regulation in Arabidopsis

    PubMed Central

    Guan, Peizhu

    2017-01-01

    In nature and agriculture, nitrate availability is a main environmental cue for plant growth, development and stress responses. Nitrate signaling and regulation are hence at the center of communications between plant intrinsic programs and the environment. It is also well known that endogenous phytohormones play numerous critical roles in integrating extrinsic cues and intrinsic responses, regulating and refining almost all aspects of plant growth, development and stress responses. Therefore, interaction between nitrate and phytohormones, such as auxins, cytokinins, abscisic acid, gibberellins, and ethylene, is prevalent. The growing evidence indicates that biosynthesis, de-conjugation, transport, and signaling of hormones are partly controlled by nitrate signaling. Recent advances with nitrate signaling and transcriptional regulation in Arabidopsis give rise to new paradigms. Given the comprehensive nitrate transport, sensing, signaling and regulations at the level of the cell and organism, nitrate itself is a local and long-distance signal molecule, conveying N status at the whole-plant level. A direct molecular link between nitrate signaling and cell cycle progression was revealed with TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1-20 (TCP20) – NIN-LIKE PROTEIN 6/7 (NLP6/7) regulatory nexus. NLPs are key regulators of nitrogen responses in plants. TCPs function as the main regulators of plant morphology and architecture, with the emerging role as integrators of plant developmental responses to the environment. By analogy with auxin being proposed as a plant morphogen, nitrate may be an environmental morphogen. The morphogen-gradient-dependent and cell-autonomous mechanisms of nitrate signaling and regulation are an integral part of cell growth and cell identification. This is especially true in root meristem growth that is regulated by intertwined nitrate, phytohormones, and glucose-TOR signaling pathways. Furthermore, the nitrate transcriptional

  6. Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network

    PubMed Central

    Sun, Shuguo; Irvine, Kenneth D.

    2016-01-01

    The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated, and to define their respective contributions in vivo. PMID:27268910

  7. Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network.

    PubMed

    Sun, Shuguo; Irvine, Kenneth D

    2016-09-01

    The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated and to define their respective contributions in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Modulating inflammation through the negative regulation of NF-κB signaling.

    PubMed

    Rothschild, Daniel E; McDaniel, Dylan K; Ringel-Scaia, Veronica M; Allen, Irving C

    2018-02-01

    Immune system activation is essential to thwart the invasion of pathogens and respond appropriately to tissue damage. However, uncontrolled inflammation can result in extensive collateral damage underlying a diverse range of auto-inflammatory, hyper-inflammatory, and neoplastic diseases. The NF-κB signaling pathway lies at the heart of the immune system and functions as a master regulator of gene transcription. Thus, this signaling cascade is heavily targeted by mechanisms designed to attenuate overzealous inflammation and promote resolution. Mechanisms associated with the negative regulation of NF-κB signaling are currently under intense investigation and have yet to be fully elucidated. Here, we provide an overview of mechanisms that negatively regulate NF-κB signaling through either attenuation of signal transduction, inhibition of posttranscriptional signaling, or interference with posttranslational modifications of key pathway components. While the regulators discussed for each group are far from comprehensive, they exemplify common mechanistic approaches that inhibit this critical biochemical signaling cascade. Despite their diversity, a commonality among these regulators is their selection of specific targets at key inflection points in the pathway, such as TNF-receptor-associated factor family members or essential kinases. A better understanding of these negative regulatory mechanisms will be essential to gain greater insight related to the maintenance of immune system homeostasis and inflammation resolution. These processes are vital elements of disease pathology and have important implications for targeted therapeutic strategies. ©2018 Society for Leukocyte Biology.

  9. MRAP2 regulates ghrelin receptor signaling and hunger sensing.

    PubMed

    Srisai, Dollada; Yin, Terry C; Lee, Abigail A; Rouault, Alix A J; Pearson, Nicole A; Grobe, Justin L; Sebag, Julien A

    2017-09-28

    Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling. We show that MRAP2 interacts with GHSR1a and potentiates ghrelin-stimulated signaling both in vitro and in vivo. We demonstrate that in the absence of MRAP2, fasting fails to activate agouti-related protein neurons. In addition, we show that the orexigenic effect of ghrelin is lost in mice lacking MRAP2. Our results suggest that MRAP2 is an important modulator of the energy homeostasis machinery that operates through the regulation of multiple GPCRs throughout the hypothalamus.Melanocortin receptor accessory protein 2 (MRAP2) is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling. Here the authors show that MRAP2 also regulates ghrelin receptor signalling in the hypothalamus and starvation sensing in mice.

  10. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu, Zhong Xin; Sun, Cong Cong; Wenzhou People's Hospital, Wenzhou, Zhejiang

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Westernmore » blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.« less

  11. Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.

    PubMed

    Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

    2014-01-01

    Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling.

  12. Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications

    PubMed Central

    Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

    2014-01-01

    Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling. PMID:25628960

  13. DEG9, a serine protease, modulates cytokinin and light signaling by regulating the level of ARABIDOPSIS RESPONSE REGULATOR 4.

    PubMed

    Chi, Wei; Li, Jing; He, Baoye; Chai, Xin; Xu, Xiumei; Sun, Xuwu; Jiang, Jingjing; Feng, Peiqiang; Zuo, Jianru; Lin, Rongcheng; Rochaix, Jean-David; Zhang, Lixin

    2016-06-21

    Cytokinin is an essential phytohormone that controls various biological processes in plants. A number of response regulators are known to be important for cytokinin signal transduction. ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4) mediates the cross-talk between light and cytokinin signaling through modulation of the activity of phytochrome B. However, the mechanism that regulates the activity and stability of ARR4 is unknown. Here we identify an ATP-independent serine protease, degradation of periplasmic proteins 9 (DEG9), which localizes to the nucleus and regulates the stability of ARR4. Biochemical evidence shows that DEG9 interacts with ARR4, thereby targeting ARR4 for degradation, which suggests that DEG9 regulates the stability of ARR4. Moreover, genetic evidence shows that DEG9 acts upstream of ARR4 and regulates the activity of ARR4 in cytokinin and light-signaling pathways. This study thus identifies a role for a ubiquitin-independent selective protein proteolysis in the regulation of the stability of plant signaling components.

  14. Hsp70-Bag3 interactions regulate cancer-related signaling networks.

    PubMed

    Colvin, Teresa A; Gabai, Vladimir L; Gong, Jianlin; Calderwood, Stuart K; Li, Hu; Gummuluru, Suryaram; Matchuk, Olga N; Smirnova, Svetlana G; Orlova, Nina V; Zamulaeva, Irina A; Garcia-Marcos, Mikel; Li, Xiaokai; Young, Z T; Rauch, Jennifer N; Gestwicki, Jason E; Takayama, Shinichi; Sherman, Michael Y

    2014-09-01

    Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here, we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70-Bag3 module is a broad-acting regulator of cancer cell signaling by modulating the activity of the transcription factors NF-κB, FoxM1, Hif1α, the translation regulator HuR, and the cell-cycle regulators p21 and survivin. We also identified a small-molecule inhibitor, YM-1, that disrupts the Hsp70-Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70-Bag3 complex may offer an appealing anticancer target. ©2014 American Association for Cancer Research.

  15. Hsp70-Bag3 interactions regulate cancer-related signaling networks

    PubMed Central

    Colvin, T.A.; Gabai, V.L.; Gong, J.; Calderwood, S.K.; Li, H.; Gummuluru, S.; Matchuk, O.N; Smirnova, S.G; Orlova, N.V; Zamulaeva, I.A; Garcia-Marcos, M.; Li, X.; Young, Z.T.; Rauch, J.N.; Gestwicki, J.E.; Takayama, S.; Sherman, M.Y.

    2014-01-01

    Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70-Bag3 module is a broad-acting regulator of cancer cell signaling, including by modulating the activity of the transcription factors NF-kB, FoxM1 and Hif1α, the translation regulator HuR and the cell cycle regulators p21 and survivin. We also identified a small molecule inhibitor, YM-1, that disrupts Hsp70-Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70-Bag3 complex may offer an appealing anti-cancer target. PMID:24994713

  16. Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward.

    PubMed

    Shen, M; Jiang, C; Liu, P; Wang, F; Ma, L

    2016-12-06

    The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure. Our results showed that inhibition of leptin signaling by intracerebroventricular infusion of the leptin receptor (LepR) antagonist SMLA during cocaine conditioning increased the cocaine-CPP and upregulated the level of dopamine and its metabolites in the nucleus accumbens (NAc). We then selectively knocked down the LepR in the mesolimbic ventral tegmental area (VTA), NAc core and central amygdala (CeA) by injecting AAV-Cre into Lepr flox/flox mice. LepR deletion in the VTA increased the dopamine levels in the NAc and enhanced the cocaine-conditioned reward. LepR deletion in the NAc core enhanced the cocaine-conditioned reward and impaired the effect of the D2-dopamine receptor on cocaine-CPP, whereas LepR deletion in the CeA had no effect on cocaine-CPP but increased the anxiety level of mice. In addition, prior exposure to saccharin increased LepR mRNA and STAT3 phosphorylation in the NAc and VTA and impaired cocaine-CPP. These results indicate that leptin signaling is critically involved in cocaine-conditioned reward and the regulation of drug reward by a natural reward and that these effects are dependent on mesolimbic LepR.

  17. Regulation of VEGF signaling by membrane traffic.

    PubMed

    Horowitz, Arie; Seerapu, Himabindu Reddy

    2012-09-01

    Recent findings have drawn attention to the role of membrane traffic in the signaling of vascular endothelial growth factor (VEGF). The significance of this development stems from the pivotal function of VEGF in vasculogenesis and angiogenesis. The outline of the regulation of VEGF receptor (VEGFR) signaling by membrane traffic is similar to that of the epidermal growth factor receptor (EGFR), a prototype of the intertwining between membrane traffic and signaling. There are, however, unique features in VEGFR signaling that are conferred in part by the involvement of the co-receptor neuropilin (Nrp). Nrp1 and VEGFR2 are integrated into membrane traffic through the adaptor protein synectin, which recruits myosin VI, a molecular motor that drives inward trafficking [17,21,64]. The recent detection of only mild vascular defects in a knockin mouse model that expresses Nrp1 lacking a cytoplasmic domain [104], questions the co-receptor's role in VEGF signaling and membrane traffic. The regulation of endocytosis by ephrin-B2 is another feature unique to VEGR2/3 [18,19], but it awaits a mechanistic explanation. Current models do not fully explain how membrane traffic bridges between VEGFR and the downstream effectors that produce its functional outcome, such as cell migration. VEGF-A appears to accomplish this task in part by recruiting endocytic vesicles carrying RhoA to internalized active VEGFR2 [58]. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. [The history of optical signals for traffic regulation].

    PubMed

    Draeger, J; Harsch, V

    2008-04-01

    For signal transmission in traffic today, different optical, acoustic, or other physical or technical means are used for information. The different kinds of traffic (water navigation, road and rail, and, later air transport) made traffic regulation necessary early on. This regulation, from its very beginning in ancient times, began by means of optical signals; nowadays, this remains the most important method. From the very start, minimum requirements for the navigator's vision, color discrimination, dark adaptation, and even visual field were needed. For historical reasons, it was in seafaring medicine that these first developed. Besides the development of the different signals, methods for checking the requirements were soon developed. National and international requirements have been very different. Only within the last 50 years has international cooperation led to the acceptance of general standards for the different traffic modes. This article discusses the technical development of optical signals for the different kinds of traffic, from ancient times to the present, and explains the development of minimum requirements for the different visual functions.

  19. Regulation from within: the cytoskeleton in transmembrane signaling

    PubMed Central

    Jaqaman, Khuloud; Grinstein, Sergio

    2013-01-01

    There is mounting evidence that the plasma membrane is highly dynamic and organized in a complex manner. The cortical cytoskeleton is proving to be a particularly important regulator of plasmalemmal organization, modulating the mobility of proteins and lipids in the membrane, facilitating their segregation and influencing their clustering. This organization plays a critical role in receptor-mediated signaling, especially in the case of immunoreceptors, which require lateral clustering for their activation. Based on recent developments, we discuss the structures and mechanisms whereby the cortical cytoskeleton regulates membrane dynamics and organization, and how the non-uniform distribution of immunoreceptors and their self-association may affect activation and signaling. PMID:22917551

  20. Ras signaling in aging and metabolic regulation.

    PubMed

    Slack, Cathy

    2017-12-07

    Aberrant signal transduction downstream of the Ras GTPase has a well-established role in tumorigenesis. Mutations that result in hyperactivation of Ras are responsible for a third of all human cancers. Hence, small molecule inhibitors of the Ras signal transduction cascade have been under intense focus as potential cancer treatments. In both invertebrate and mammalian models, emerging evidence has also implicated components of the Ras signaling pathway in aging and metabolic regulation. Here, I review the current evidence for Ras signaling in these newly discovered roles highlighting the interactions between the Ras pathway and other longevity assurance mechanisms. Defining the role of Ras signaling in maintaining age-related health may have important implications for the development of interventions that could not only increase lifespan but also delay the onset and/or progression of age-related functional decline.

  1. Nuclear movement regulated by non-Smad Nodal signaling via JNK is associated with Smad signaling during zebrafish endoderm specification.

    PubMed

    Hozumi, Shunya; Aoki, Shun; Kikuchi, Yutaka

    2017-11-01

    Asymmetric nuclear positioning is observed during animal development, but its regulation and significance in cell differentiation remain poorly understood. Using zebrafish blastulae, we provide evidence that nuclear movement towards the yolk syncytial layer, which comprises extraembryonic tissue, occurs in the first cells fated to differentiate into the endoderm. Nodal signaling is essential for nuclear movement, whereas nuclear envelope proteins are involved in movement through microtubule formation. Positioning of the microtubule-organizing center, which is proposed to be crucial for nuclear movement, is regulated by Nodal signaling and nuclear envelope proteins. The non-Smad JNK signaling pathway, which is downstream of Nodal signaling, regulates nuclear movement independently of the Smad pathway, and this nuclear movement is associated with Smad signal transduction toward the nucleus. Our study provides insight into the function of nuclear movement in Smad signaling toward the nucleus, and could be applied to the control of TGFβ signaling. © 2017. Published by The Company of Biologists Ltd.

  2. Pulsatile Hormonal Signaling to Extracellular Signal-regulated Kinase

    PubMed Central

    Perrett, Rebecca M.; Voliotis, Margaritis; Armstrong, Stephen P.; Fowkes, Robert C.; Pope, George R.; Tsaneva-Atanasova, Krasimira; McArdle, Craig A.

    2014-01-01

    Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses that stimulate synthesis and secretion of pituitary gonadotropin hormones and thereby mediate control of reproduction. It acts via G-protein-coupled receptors to stimulate effectors, including ERK. Information could be encoded in GnRH pulse frequency, width, amplitude, or other features of pulse shape, but the relative importance of these features is unknown. Here we examine this using automated fluorescence microscopy and mathematical modeling, focusing on ERK signaling. The simplest scenario is one in which the system is linear, and response dynamics are relatively fast (compared with the signal dynamics). In this case integrated system output (ERK activation or ERK-driven transcription) will be roughly proportional to integrated input, but we find that this is not the case. Notably, we find that relatively slow response kinetics lead to ERK activity beyond the GnRH pulse, and this reduces sensitivity to pulse width. More generally, we show that the slowing of response kinetics through the signaling cascade creates a system that is robust to pulse width. We, therefore, show how various levels of response kinetics synergize to dictate system sensitivity to different features of pulsatile hormone input. We reveal the mathematical and biochemical basis of a dynamic GnRH signaling system that is robust to changes in pulse amplitude and width but is sensitive to changes in receptor occupancy and frequency, precisely the features that are tightly regulated and exploited to exert physiological control in vivo. PMID:24482225

  3. Preoptic leptin signaling modulates energy balance independent of body temperature regulation.

    PubMed

    Yu, Sangho; Cheng, Helia; François, Marie; Qualls-Creekmore, Emily; Huesing, Clara; He, Yanlin; Jiang, Yanyan; Gao, Hong; Xu, Yong; Zsombok, Andrea; Derbenev, Andrei V; Nillni, Eduardo A; Burk, David H; Morrison, Christopher D; Berthoud, Hans-Rudolf; Münzberg, Heike

    2018-05-15

    The adipokine leptin acts on the brain to regulate energy balance but specific functions in many brain areas remain poorly understood. Among these, the preoptic area (POA) is well known to regulate core body temperature by controlling brown fat thermogenesis, and we have previously shown that glutamatergic, long-form leptin receptor (Lepr)-expressing neurons in the POA are stimulated by warm ambient temperature and suppress energy expenditure and food intake. Here we further investigate the role of POA leptin signaling in body weight regulation and its relationship to body temperature regulation in mice. We show that POA Lepr signaling modulates energy expenditure in response to internal energy state, and thus contributes to body weight homeostasis. However, POA leptin signaling is not involved in ambient temperature-dependent metabolic adaptations. Our study reveals a novel cell population through which leptin regulates body weight. © 2018, Yu et al.

  4. Conserved Insulin Signaling in the Regulation of Oocyte Growth, Development, and Maturation

    PubMed Central

    DAS, DEBABRATA; ARUR, SWATHI

    2017-01-01

    Insulin signaling regulates various aspects of physiology, such as glucose homeostasis and aging, and is a key determinant of female reproduction in metazoans. That insulin signaling is crucial for female reproductive health is clear from clinical data linking hyperinsulinemic and hypoinsulinemic condition with certain types of ovarian dysfunction, such as altered steroidogenesis, polycystic ovary syndrome, and infertility. Thus, understanding the signaling mechanisms that underlie the control of insulin-mediated ovarian development is important for the accurate diagnosis of and intervention for female infertility. Studies of invertebrate and vertebrate model systems have revealed the molecular determinants that transduce insulin signaling as well as which biological processes are regulated by the insulin-signaling pathway. The molecular determinants of the insulin-signaling pathway, from the insulin receptor to its downstream signaling components, are structurally and functionally conserved across evolution, from worms to mammals – yet, physiological differences in signaling still exist. Insulin signaling acts cooperatively with gonadotropins in mammals and lower vertebrates to mediate various aspects of ovarian development, mainly owing to evolution of the endocrine system in vertebrates. In contrast, insulin signaling in Drosophila and Caenorhabditis elegans directly regulates oocyte growth and maturation. In this review, we compare and contrast insulin-mediated regulation of ovarian functions in mammals, lower vertebrates, C. elegans, and Drosophila, and highlight conserved signaling pathways and regulatory mechanisms in general while illustrating insulin’s unique role in specific reproductive processes. PMID:28379636

  5. Endocardial Hippo signaling regulates myocardial growth and cardiogenesis.

    PubMed

    Artap, Stanley; Manderfield, Lauren J; Smith, Cheryl L; Poleshko, Andrey; Aghajanian, Haig; See, Kelvin; Li, Li; Jain, Rajan; Epstein, Jonathan A

    2018-08-01

    The Hippo signaling pathway has been implicated in control of cell and organ size, proliferation, and endothelial-mesenchymal transformation. This pathway impacts upon two partially redundant transcription cofactors, Yap and Taz, that interact with other factors, including members of the Tead family, to affect expression of downstream genes. Yap and Taz have been shown to regulate, in a cell-autonomous manner, myocardial proliferation, myocardial hypertrophy, regenerative potential, and overall size of the heart. Here, we show that Yap and Taz also play an instructive, non-cell-autonomous role in the endocardium of the developing heart to regulate myocardial growth through release of the paracrine factor, neuregulin. Without endocardial Yap and Taz, myocardial growth is impaired causing early post-natal lethality. Thus, the Hippo signaling pathway regulates cell size via both cell-autonomous and non-cell-autonomous mechanisms. Furthermore, these data suggest that Hippo may regulate organ size via a sensing and paracrine function in endothelial cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression

    PubMed Central

    Suzuki, Tomoyuki; Dai, Ping; Hatakeyama, Tomoya; Harada, Yoshinori; Tanaka, Hideo; Yoshimura, Norio; Takamatsu, Tetsuro

    2013-01-01

    Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic β-cell line, to TGF-β signaling. We found that inhibition of TGF-β signaling promotes proliferation of the cells significantly, while TGF-β signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-β signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-β signaling. Our data show that TGF-β signaling mediates the cell-cycle progression of pancreatic β-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-β signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of β-cells. PMID:23720603

  7. Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baker, Anna W.; Satyshur, Kenneth A.; Moreno Morales, Neydis

    2016-02-01

    ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulatormore » (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCEBphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of

  8. Negative regulators of the RIG-I-like receptor signaling pathway

    PubMed Central

    Quicke, Kendra M.; Diamond, Michael S.; Suthar, Mehul S.

    2017-01-01

    SUMMARY Upon recognition of specific molecular patterns on viruses, bacteria and fungi, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFN), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of the immune response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage. An over-exuberant innate immune response can lead to the destruction of cells and tissues, and the development of spontaneous autoimmunity. The RIG-I-like receptors (RLRs) retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) belong to a family of cytosolic host RNA helicases that recognize distinct non-self RNA signatures and trigger innate immune responses against several RNA virus infections. The RLR signaling pathway is tightly regulated to achieve a well-orchestrated response aimed at maximizing antiviral immunity and minimizing immune-mediated pathology. This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG-I, MDA5 and MAVS function. PMID:28295214

  9. Signaling Pathways Involved in the Regulation of mRNA Translation

    PubMed Central

    2018-01-01

    ABSTRACT Translation is a key step in the regulation of gene expression and one of the most energy-consuming processes in the cell. In response to various stimuli, multiple signaling pathways converge on the translational machinery to regulate its function. To date, the roles of phosphoinositide 3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK) pathways in the regulation of translation are among the best understood. Both pathways engage the mechanistic target of rapamycin (mTOR) to regulate a variety of components of the translational machinery. While these pathways regulate protein synthesis in homeostasis, their dysregulation results in aberrant translation leading to human diseases, including diabetes, neurological disorders, and cancer. Here we review the roles of the PI3K/AKT and MAPK pathways in the regulation of mRNA translation. We also highlight additional signaling mechanisms that have recently emerged as regulators of the translational apparatus. PMID:29610153

  10. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.

    PubMed

    Straub, Adam C; Lohman, Alexander W; Billaud, Marie; Johnstone, Scott R; Dwyer, Scott T; Lee, Monica Y; Bortz, Pamela Schoppee; Best, Angela K; Columbus, Linda; Gaston, Benjamin; Isakson, Brant E

    2012-11-15

    Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle. Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) α (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb α and is abrogated by its genetic depletion. Mechanistically, endothelial Hb α haem iron in the Fe(3+) state permits NO signalling, and this signalling is shut off when Hb α is reduced to the Fe(2+) state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb α oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells.

  11. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Yi-Ting; Ding, Jing-Ya; Li, Ming-Yang

    2012-09-10

    Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model tomore » study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the

  12. Signaling hierarchy regulating human endothelial cell development

    USDA-ARS?s Scientific Manuscript database

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  13. Post-transcriptional regulation of ethylene perception and signaling in Arabidopsis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schaller, George Eric

    2014-03-19

    The simple gas ethylene functions as an endogenous regulator of plant growth and development, and modulates such energy relevant processes as photosynthesis and biomass accumulation. Ethylene is perceived in the plant Arabidopsis by a five-member family of receptors related to bacterial histidine kinases. Our data support a general model in which the receptors exist as parts of larger protein complexes. Our goals have been to (1) characterize physical interactions among members of the signaling complex; (2) the role of histidine-kinase transphosphorylation in signaling by the complex; and (3) the role of a novel family of proteins that regulate signal outputmore » by the receptors.« less

  14. GDSL LIPASE1 Modulates Plant Immunity through Feedback Regulation of Ethylene Signaling1[W

    PubMed Central

    Kim, Hye Gi; Kwon, Sun Jae; Jang, Young Jin; Nam, Myung Hee; Chung, Joo Hee; Na, Yun-Cheol; Guo, Hongwei; Park, Ohkmae K.

    2013-01-01

    Ethylene is a key signal in the regulation of plant defense responses. It is required for the expression and function of GDSL LIPASE1 (GLIP1) in Arabidopsis (Arabidopsis thaliana), which plays an important role in plant immunity. Here, we explore molecular mechanisms underlying the relationship between GLIP1 and ethylene signaling by an epistatic analysis of ethylene response mutants and GLIP1-overexpressing (35S:GLIP1) plants. We show that GLIP1 expression is regulated by ethylene signaling components and, further, that GLIP1 expression or application of petiole exudates from 35S:GLIP1 plants affects ethylene signaling both positively and negatively, leading to ETHYLENE RESPONSE FACTOR1 activation and ETHYLENE INSENSITIVE3 (EIN3) down-regulation, respectively. Additionally, 35S:GLIP1 plants or their exudates increase the expression of the salicylic acid biosynthesis gene SALICYLIC ACID INDUCTION-DEFICIENT2, known to be inhibited by EIN3 and EIN3-LIKE1. These results suggest that GLIP1 regulates plant immunity through positive and negative feedback regulation of ethylene signaling, and this is mediated by its activity to accumulate a systemic signal(s) in the phloem. We propose a model explaining how GLIP1 regulates the fine-tuning of ethylene signaling and ethylene-salicylic acid cross talk. PMID:24170202

  15. Canonical Wnt signaling in megakaryocytes regulates proplatelet formation

    PubMed Central

    Macaulay, Iain C.; Thon, Jonathan N.; Tijssen, Marloes R.; Steele, Brian M.; MacDonald, Bryan T.; Meade, Gerardene; Burns, Philippa; Rendon, Augusto; Salunkhe, Vishal; Murphy, Ronan P.; Bennett, Cavan; Watkins, Nicholas A.; He, Xi; Fitzgerald, Desmond J.; Italiano, Joseph E.

    2013-01-01

    Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in β-catenin expression. β-catenin accumulation was inhibited by the canonical antagonist dickkopf-1 (DKK1) and by the noncanonical agonist Wnt5a. Whole genome expression analysis demonstrated that Wnt3a and Wnt5a regulated distinct patterns of gene expression in MKs, and revealed a further interplay between canonical and noncanonical Wnt pathways. Fetal liver cells derived from low-density-lipoprotein receptor-related protein 6-deficient mice (LRP6−/−), generated dramatically reduced numbers of MKs in culture of lower ploidy (2N and 4N) than wild-type controls, implicating LRP6-dependent Wnt signaling in MK proliferation and maturation. Finally, in wild-type mature murine fetal liver-derived MKs, Wnt3a potently induced proplatelet formation, an effect that could be completely abrogated by DKK1. These data identify novel extrinsic regulators of proplatelet formation, and reveal a profound role for Wnt signaling in platelet production. PMID:23160460

  16. Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum

    PubMed Central

    Echevarría, Wihelma; Leite, M. Fatima; Guerra, Mateus T.; Zipfel, Warren R.; Nathanson, Michael H.

    2013-01-01

    Calcium is a second messenger in virtually all cells and tissues1. Calcium signals in the nucleus have effects on gene transcription and cell growth that are distinct from those of cytosolic calcium signals; however, it is unknown how nuclear calcium signals are regulated. Here we identify a reticular network of nuclear calcium stores that is continuous with the endoplasmic reticulum and the nuclear envelope. This network expresses inositol 1,4,5-trisphosphate (InsP3) receptors, and the nuclear component of InsP3-mediated calcium signals begins in its locality. Stimulation of these receptors with a little InsP3 results in small calcium signals that are initiated in this region of the nucleus. Localized release of calcium in the nucleus causes nuclear protein kinase C (PKC) to translocate to the region of the nuclear envelope, whereas release of calcium in the cytosol induces translocation of cytosolic PKC to the plasma membrane. Our findings show that the nucleus contains a nucleoplasmic reticulum with the capacity to regulate calcium signals in localized subnuclear regions. The presence of such machinery provides a potential mechanism by which calcium can simultaneously regulate many independent processes in the nucleus. PMID:12717445

  17. The emerging role of Hippo signaling pathway in regulating osteoclast formation.

    PubMed

    Yang, Wanlei; Han, Weiqi; Qin, An; Wang, Ziyi; Xu, Jiake; Qian, Yu

    2018-06-01

    A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis. It is revealed that specific molecules of the Hippo-signaling pathway take part in a stage specific regulation in pre-osteoclast proliferation, osteoclast differentiation and osteoclast apoptosis and survival. Upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors, and influence osteoclast differentiation via regulating the expression of downstream target genes such as connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition, through interacting or cross talking with RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function. Elucidating the roles of the Hippo-signaling pathway in osteoclast development and specific molecules involved is important for understanding the mechanism of bone homeostasis and diseases. © 2017 Wiley Periodicals, Inc.

  18. Signaling coupled epigenomic regulation of gene expression.

    PubMed

    Kumar, R; Deivendran, S; Santhoshkumar, T R; Pillai, M R

    2017-10-26

    Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently translate upstream signals into post-translational modifications (PTMs) on histones and coregulators such as corepressors, coactivators, DNA-binding factors and PTM modifying enzymes. Because a protein with multiple residues for putative PTMs is expected to undergo more than one PTM in cells stimulated with growth factors, the outcome of combinational PTM codes on histones and coregulators is profoundly shaped by regulatory interplays between PTMs. The genomic functions of signaling kinases in cancer cells are manifested by the downstream effectors of cytoplasmic signaling cascades as well as translocation of the cytoplasmic signaling kinases to the nucleus. Signaling-mediated phosphorylation of histones serves as a regulatory switch for other PTMs, and connects chromatin remodeling complexes into gene transcription and gene activity. Here, we will discuss the recent advances in signaling-dependent epigenomic regulation of gene transcription using a few representative cancer-relevant serine/threonine and tyrosine kinases and their interplay with chromatin remodeling factors in cancer cells.

  19. Gravity-regulated gene expression in Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Sederoff, Heike; Brown, Christopher S.; Heber, Steffen; Kajla, Jyoti D.; Kumar, Sandeep; Lomax, Terri L.; Wheeler, Benjamin; Yalamanchili, Roopa

    Plant growth and development is regulated by changes in environmental signals. Plants sense environmental changes and respond to them by modifying gene expression programs to ad-just cell growth, differentiation, and metabolism. Functional expression of genes comprises many different processes including transcription, translation, post-transcriptional and post-translational modifications, as well as the degradation of RNA and proteins. Recently, it was discovered that small RNAs (sRNA, 18-24 nucleotides long), which are heritable and systemic, are key elements in regulating gene expression in response to biotic and abiotic changes. Sev-eral different classes of sRNAs have been identified that are part of a non-cell autonomous and phloem-mobile network of regulators affecting transcript stability, translational kinetics, and DNA methylation patterns responsible for heritable transcriptional silencing (epigenetics). Our research has focused on gene expression changes in response to gravistimulation of Arabidopsis roots. Using high-throughput technologies including microarrays and 454 sequencing, we iden-tified rapid changes in transcript abundance of genes as well as differential expression of small RNA in Arabidopsis root apices after minutes of reorientation. Some of the differentially regu-lated transcripts are encoded by genes that are important for the bending response. Functional mutants of those genes respond faster to reorientation than the respective wild type plants, indicating that these proteins are repressors of differential cell elongation. We compared the gravity responsive sRNAs to the changes in transcript abundances of their putative targets and identified several potential miRNA: target pairs. Currently, we are using mutant and transgenic Arabidopsis plants to characterize the function of those miRNAs and their putative targets in gravitropic and phototropic responses in Arabidopsis.

  20. Tissue-specific Insulin Signaling in the Regulation of Metabolism and Aging

    PubMed Central

    Zhang, Jingjing

    2014-01-01

    In mammals, insulin signaling regulates glucose homeostasis and plays an essential role in metabolism, organ growth, development, fertility, and lifespan. Defects in this signaling pathway contribute to various metabolic diseases such as type 2 diabetes, polycystic ovarian disease, hypertension, hyperlipidemia, and atherosclerosis. However, reducing the insulin signaling pathway has been found to increase longevity and delay the aging-associated diseases in various animals, ranging from nematodes to mice. These seemly paradoxical findings raise an interesting question as to how modulation of the insulin signaling pathway could be an effective approach to improve metabolism and aging. In this review, we summarize current understanding on tissue-specific functions of insulin signaling in the regulation of metabolism and lifespan. We also discuss potential benefits and limitations in modulating tissue-specific insulin signaling pathway to improve metabolism and healthspan. PMID:25087968

  1. Gene Regulation and Signal Transduction in the ICE-CBF-COR Signaling Pathway during Cold Stress in Plants.

    PubMed

    Wang, Da-Zhi; Jin, Ya-Nan; Ding, Xi-Han; Wang, Wen-Jia; Zhai, Shan-Shan; Bai, Li-Ping; Guo, Zhi-Fu

    2017-10-01

    Low temperature is an abiotic stress that adversely affects the growth and production of plants. Resistance and adaptation of plants to cold stress is dependent upon the activation of molecular networks and pathways involved in signal transduction and the regulation of cold-stress related genes. Because it has numerous and complex genes, regulation factors, and pathways, research on the ICE-CBF-COR signaling pathway is the most studied and detailed, which is thought to be rather important for cold resistance of plants. In this review, we focus on the function of each member, interrelation among members, and the influence of manipulators and repressors in the ICE-CBF-COR pathway. In addition, regulation and signal transduction concerning plant hormones, circadian clock, and light are discussed. The studies presented provide a detailed picture of the ICE-CBF-COR pathway.

  2. Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2

    PubMed Central

    Han, Myoung-Eun; Lee, Young-Suk; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae-Ock

    2009-01-01

    Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. PMID:19742123

  3. Dopamine Signaling Regulates Fat Content through β-Oxidation in Caenorhabditis elegans

    PubMed Central

    Barros, Alexandre Guimarães de Almeida; Bridi, Jessika Cristina; de Souza, Bruno Rezende; de Castro Júnior, Célio; de Lima Torres, Karen Cecília; Malard, Leandro; Jorio, Ado; de Miranda, Débora Marques; Ashrafi, Kaveh; Romano-Silva, Marco Aurélio

    2014-01-01

    The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots. PMID:24465759

  4. Hippo Signaling Regulates Pancreas Development through Inactivation of Yap

    PubMed Central

    Day, Caroline E.; Boerner, Brian P.; Johnson, Randy L.; Sarvetnick, Nora E.

    2012-01-01

    The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition, and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo kinase cascade is a critical regulator of organ growth. To investigate the role of Hippo signaling in pancreas biology, we deleted Hippo pathway components in the developing mouse pancreas. Unexpectedly, the pancreas from Hippo-deficient offspring was reduced in size, with defects evident throughout the organ. Increases in the dephosphorylated nuclear form of Yap are apparent throughout the exocrine compartment and correlate with increases in levels of cell proliferation. However, the mutant exocrine tissue displays extensive disorganization leading to pancreatitis-like autodigestion. Interestingly, our results suggest that Hippo signaling does not directly regulate the pancreas endocrine compartment as Yap expression is lost following endocrine specification through a Hippo-independent mechanism. Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ. PMID:23071096

  5. Retinal Determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by Master Regulators

    PubMed Central

    Baker, Nicholas E.; Firth, Lucy C.

    2015-01-01

    It is thought that Retinal Determination gene products define the response made to cell-cell signals within the eye developmental field by binding to enhancers of genes that are also regulated by cell-cell signaling pathways. In Drosophila, Retinal Determination genes including Eyeless, teashirt, eyes absent, dachsous and sine oculis, are required for normal eye development and can induce ectopic eyes when mis-expressed. Characterization of the enhancers responsible for eye expression of the hedgehog, shaven, and atonal genes, as well as the dynamics of Retinal Determination gene expression themselves, now suggest a multilayered network whereby transcriptional regulation by either Retinal Determination genes or cell-cell signaling pathways can sometimes be indirect and mediated by other transcription factor intermediates. In this updated view of the interaction between extracellular information and cell intrinsic programs during development, regulation of individual genes might sometimes be several steps removed from either the Retinal Determination genes or cell-cell signaling pathways that nevertheless govern their expression. PMID:21607995

  6. FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation.

    PubMed

    Crowley, Jenni E; Stadanlick, Jason E; Cambier, John C; Cancro, Michael P

    2009-02-12

    These studies investigate how interactions between the BCR and FcgammaRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcgammaRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and FcgammaRIIB coligation, and optimal action relies on the Src-homology-2 (SH2)-containing inositol 5 phosphase-1 (SHIP1). Subsequent to FcgammaRIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-kappaB activation, and Bcl-xL levels. These findings link the negative regulatory functions of FcgammaRIIB with BLyS-mediated B-cell survival.

  7. The Spectrin cytoskeleton regulates the Hippo signalling pathway.

    PubMed

    Fletcher, Georgina C; Elbediwy, Ahmed; Khanal, Ichha; Ribeiro, Paulo S; Tapon, Nic; Thompson, Barry J

    2015-04-01

    The Spectrin cytoskeleton is known to be polarised in epithelial cells, yet its role remains poorly understood. Here, we show that the Spectrin cytoskeleton controls Hippo signalling. In the developing Drosophila wing and eye, loss of apical Spectrins (alpha/beta-heavy dimers) produces tissue overgrowth and mis-regulation of Hippo target genes, similar to loss of Crumbs (Crb) or the FERM-domain protein Expanded (Ex). Apical beta-heavy Spectrin binds to Ex and co-localises with it at the apical membrane to antagonise Yki activity. Interestingly, in both the ovarian follicular epithelium and intestinal epithelium of Drosophila, apical Spectrins and Crb are dispensable for repression of Yki, while basolateral Spectrins (alpha/beta dimers) are essential. Finally, the Spectrin cytoskeleton is required to regulate the localisation of the Hippo pathway effector YAP in response to cell density human epithelial cells. Our findings identify both apical and basolateral Spectrins as regulators of Hippo signalling and suggest Spectrins as potential mechanosensors. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  8. Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators

    PubMed Central

    Whittington, Miles A.; Kopell, Nancy J.

    2015-01-01

    The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID:26558772

  9. A Discrete Ubiquitin-Mediated Network Regulates the Strength of NOD2 Signaling

    PubMed Central

    Tigno-Aranjuez, Justine T.; Bai, Xiaodong

    2013-01-01

    Dysregulation of NOD2 signaling is implicated in the pathology of various inflammatory diseases, including Crohn's disease, asthma, and sarcoidosis, making signaling proteins downstream of NOD2 potential therapeutic targets. Inhibitor-of-apoptosis (IAP) proteins, particularly cIAP1, are essential mediators of NOD2 signaling, and in this work, we describe a molecular mechanism for cIAP1's regulation in the NOD2 signaling pathway. While cIAP1 promotes RIP2's tyrosine phosphorylation and subsequent NOD2 signaling, this positive regulation is countered by another E3 ubiquitin ligase, ITCH, through direct ubiquitination of cIAP1. This ITCH-mediated ubiquitination leads to cIAP1's lysosomal degradation. Pharmacologic inhibition of cIAP1 expression in ITCH−/− macrophages attenuates heightened ITCH−/− macrophage muramyl dipeptide-induced responses. Transcriptome analysis, combined with pharmacologic inhibition of cIAP1, further defines specific pathways within the NOD2 signaling pathway that are targeted by cIAP1. This information provides genetic signatures that may be useful in repurposing cIAP1-targeted therapies to correct NOD2-hyperactive states and identifies a ubiquitin-regulated signaling network centered on ITCH and cIAP1 that controls the strength of NOD2 signaling. PMID:23109427

  10. Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.

    PubMed

    Maesako, Masato; Uemura, Kengo; Kubota, Masakazu; Ando, Koichi; Kuzuya, Akira; Asada, Megumi; Kihara, Takeshi; Kinoshita, Ayae

    2010-10-15

    Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization. 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Strigolactone regulates shoot development through a core signalling pathway

    PubMed Central

    Müller, Dörte

    2016-01-01

    ABSTRACT Strigolactones are a recently identified class of hormone that regulate multiple aspects of plant development. The DWARF14 (D14) α/β fold protein has been identified as a strigolactone receptor, which can act through the SCFMAX2 ubiquitin ligase, but the universality of this mechanism is not clear. Multiple proteins have been suggested as targets for strigolactone signalling, including both direct proteolytic targets of SCFMAX2, and downstream targets. However, the relevance and importance of these proteins to strigolactone signalling in many cases has not been fully established. Here we assess the contribution of these targets to strigolactone signalling in adult shoot developmental responses. We find that all examined strigolactone responses are regulated by SCFMAX2 and D14, and not by other D14-like proteins. We further show that all examined strigolactone responses likely depend on degradation of SMXL proteins in the SMXL6 clade, and not on the other proposed proteolytic targets BES1 or DELLAs. Taken together, our results suggest that in the adult shoot, the dominant mode of strigolactone signalling is D14-initiated, MAX2-mediated degradation of SMXL6-related proteins. We confirm that the BRANCHED1 transcription factor and the PIN-FORMED1 auxin efflux carrier are plausible downstream targets of this pathway in the regulation of shoot branching, and show that BRC1 likely acts in parallel to PIN1. PMID:27793831

  12. Phototrophy and starvation-based induction of autophagy upon removal of Gcn5-catalyzed acetylation of Atg7 in Magnaporthe oryzae.

    PubMed

    Zhang, Shulin; Liang, Meiling; Naqvi, Naweed I; Lin, Chaoxiang; Qian, Wanqiang; Zhang, Lian-Hui; Deng, Yi Zhen

    2017-08-03

    Magnaporthe oryzae, the ascomycete fungus that causes rice blast disease, initiates conidiation in response to light when grown on Prune-Agar medium containing both carbon and nitrogen sources. Macroautophagy/autophagy was shown to be essential for M. oryzae conidiation and induced specifically upon exposure to light but is undetectable in the dark. Therefore, it is inferred that autophagy is naturally induced by light, rather than by starvation during M. oryzae conidiation. However, the signaling pathway(s) involved in such phototropic induction of autophagy remains unknown. We identified an M. oryzae ortholog of GCN5 (MGG_03677), encoding a histone acetyltransferase (HAT) that negatively regulates light- and nitrogen-starvation-induced autophagy, by acetylating the autophagy protein Atg7. Furthermore, we unveiled novel regulatory mechanisms on Gcn5 at both transcriptional and post-translational levels, governing its function associated with the unique phototropic response of autophagy in this pathogenic fungus. Thus, our study depicts a signaling network and regulatory mechanism underlying the autophagy induction by important environmental clues such as light and nutrients.

  13. Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development.

    PubMed

    He, Hua; Huang, Meina; Sun, Shenfei; Wu, Yihui; Lin, Xinhua

    2017-08-01

    The tree-like structure of the mammalian lung is generated from branching morphogenesis, a reiterative process that is precisely regulated by numerous factors. How the cell surface and extra cellular matrix (ECM) molecules regulate this process is still poorly understood. Herein, we show that epithelial deletion of Heparan Sulfate (HS) synthetase Ext1 resulted in expanded branching tips and reduced branching number, associated with several mesenchymal developmental defects. We further demonstrate an expanded Fgf10 expression and increased FGF signaling activity in Ext1 mutant lungs, suggesting a cell non-autonomous mechanism. Consistent with this, we observed reduced levels of SHH signaling which is responsible for suppressing Fgf10 expression. Moreover, reactivating SHH signaling in mutant lungs rescued the tip dilation phenotype and attenuated FGF signaling. Importantly, the reduced SHH signaling activity did not appear to be caused by decreased Shh expression or protein stability; instead, biologically active form of SHH proteins were reduced in both the Ext1 mutant epithelium and surrounding wild type mesenchymal cells. Together, our study highlights the epithelial HS as a key player for dictating SHH signaling critical for lung morphogenesis.

  14. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function

    PubMed Central

    Smith, Gina A.; Fearnley, Gareth W.; Abdul-Zani, Izma; Wheatcroft, Stephen B.; Tomlinson, Darren C.; Harrison, Michael A.

    2017-01-01

    ABSTRACT Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response. PMID:28798148

  15. Orbital experiment ``Gravisensor'': phototropic reactions of the moss Physcomitrella patens to different types of LED lighting.

    NASA Astrophysics Data System (ADS)

    Nikitin, Vladimir; Berkovich, Yuliy A.; Skripnikov, Alexander; Zyablova, Natalya; Mukhoyan, Makar; Emelianov, Grigory

    the light source was maximal (about 90º) with white lighting, and somewhat smaller with 730 nm. Under red and blue light the angle of phototropic inclination was difficult to measure due to poor growth of the shoots.In ground control the growth rate under blue light was several times higher, than in flight and final degree of inclination of the shoot tip came to about 10º. In ground control under side red lighting the growth was weak, while demonstrating a pronounced phototropic bend of 90º. In ground control in the dark a vertical growth of one shoot was observed with the rate somewhat larger, than in flight variant. Data on the dynamics of inclination of experimental and control plants are presented. The acquired data will be used to analyse the mechanisms of phototropic growth changes of moss shoots.

  16. JAK/Stat signaling regulates heart precursor diversification in Drosophila

    PubMed Central

    Johnson, Aaron N.; Mokalled, Mayssa H.; Haden, Tom N.; Olson, Eric N.

    2011-01-01

    Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development. Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. Using strong Stat92E loss-of-function alleles, we show that the JAK/Stat pathway regulates tin expression prior to heart precursor cell diversification. tin expression can be subdivided into four phases and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the dorsal mesoderm does not restrict to the constrained phase 3 pattern. These embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals activate E(spl)-C genes to restrict Tin expression and the subsequent expression of the T-box transcription factor H15 to direct heart precursor diversification. This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain. PMID:21965617

  17. CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling

    PubMed Central

    Müller, Jennifer; Obermeier, Ingrid; Wöhner, Miriam; Brandl, Carolin; Mrotzek, Sarah; Angermüller, Sieglinde; Maity, Palash C.; Reth, Michael; Nitschke, Lars

    2013-01-01

    A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca2+ signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca2+ signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca2+ responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity. PMID:23836650

  18. CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling.

    PubMed

    Müller, Jennifer; Obermeier, Ingrid; Wöhner, Miriam; Brandl, Carolin; Mrotzek, Sarah; Angermüller, Sieglinde; Maity, Palash C; Reth, Michael; Nitschke, Lars

    2013-07-23

    A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca(2+) signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca(2+) signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca(2+) responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity.

  19. Phytohormones signaling and crosstalk regulating leaf angle in rice.

    PubMed

    Luo, Xiangyu; Zheng, Jingsheng; Huang, Rongyu; Huang, Yumin; Wang, Houcong; Jiang, Liangrong; Fang, Xuanjun

    2016-12-01

    Leaf angle is an important agronomic trait in rice (Oryza sativa L.). It affects both the efficiency of sunlight capture and nitrogen reservoirs. The erect leaf phenotype is suited for high-density planting and thus increasing crop yields. Many genes regulate leaf angle by affecting leaf structure, such as the lamina joint, mechanical tissues, and the midrib. Signaling of brassinosteroids (BR), auxin (IAA), and gibberellins (GA) plays important roles in the regulation of lamina joint bending in rice. In addition, the biosynthesis and signaling of BR are known to have dominant effects on leaf angle development. In this review, we summarize the factors and genes associated with the development of leaf angle in rice, outline the regulatory mechanisms based on the signaling of BR, IAA, and GA, and discuss the contribution of crosstalk between BR and IAA or GA in the formation of leaf angle. Promising lines of research in the transgenic engineering of rice leaf angle to increase grain yield are proposed.

  20. Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.

    PubMed

    Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

    2017-03-01

    During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches.

  1. Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling

    PubMed Central

    Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

    2017-01-01

    During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches. PMID:28248965

  2. Phototropic growth in a reef flat acroporid branching coral species.

    PubMed

    Kaniewska, Paulina; Campbell, Paul R; Fine, Maoz; Hoegh-Guldberg, Ove

    2009-03-01

    Many terrestrial plants form complex morphological structures and will alter these growth patterns in response to light direction. Similarly reef building corals have high morphological variation across coral families, with many species also displaying phenotypic plasticity across environmental gradients. In particular, the colony geometry in branching corals is altered by the frequency, location and direction of branch initiation and growth. This study demonstrates that for the branching species Acropora pulchra, light plays a key role in axial polyp differentiation and therefore axial corallite development--the basis for new branch formation. A. pulchra branches exhibited a directional growth response, with axial corallites only developing when light was available, and towards the incident light. Field experimentation revealed that there was a light intensity threshold of 45 micromol m(-2) s(-1), below which axial corallites would not develop and this response was blue light (408-508 nm) dependent. There was a twofold increase in axial corallite growth above this light intensity threshold and a fourfold increase in axial corallite growth under the blue light treatment. These features of coral branch growth are highly reminiscent of the initiation of phototropic branch growth in terrestrial plants, which is directed by the blue light component of sunlight.

  3. Myostatin signaling regulates Akt activity via the regulation of miR-486 expression.

    PubMed

    Hitachi, Keisuke; Nakatani, Masashi; Tsuchida, Kunihiro

    2014-02-01

    Myostatin, also known as growth and differentiation factor-8, is a pivotal negative regulator of skeletal muscle mass and reduces muscle protein synthesis by inhibiting the insulin-like growth factor-1 (IGF-1)/Akt/mammalian target of rapamycin (mTOR) pathway. However, the precise mechanism by which myostatin inhibits the IGF-1/Akt/mTOR pathway remains unclear. In this study, we investigated the global microRNA expression profile in myostatin knockout mice and identified miR-486, a positive regulator of the IGF-1/Akt pathway, as a novel target of myostatin signaling. In myostatin knockout mice, the expression level of miR-486 in skeletal muscle was significantly increased. In addition, we observed increased expression of the primary transcript of miR-486 (pri-miR-486) and Ankyrin 1.5 (Ank1.5), the host gene of miR-486, in myostatin knockout mice. In C2C12 cells, myostatin negatively regulated the expression of Ank1.5. Moreover, canonical myostatin signaling repressed the skeletal muscle-specific promoter activity of miR-486/Ank1.5. This repression was partially mediated by the E-box elements in the proximal region of the promoter. We also show that overexpression of miR-486 induced myotube hypertrophy in vitro and that miR-486 was essential to maintain skeletal muscle size both in vitro and in vivo. In addition, inhibition of miR-486 led to a decrease in Akt activity in C2C12 myotubes. Our findings indicate that miR-486 is one of the intermediary molecules connecting myostatin signaling and the IGF-1/Akt/mTOR pathway in the regulation of skeletal muscle size. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shibuya, Masabumi; Claesson-Welsh, Lena

    2006-03-10

    The VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates. VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). VEGFR1, which occurs in transmembrane and soluble forms, negatively regulates vasculogenesis and angiogenesis during early embryogenesis, but it also acts as a positive regulator of angiogenesis and inflammatory responses, playing a role in several human diseases such as rheumatoid arthritis and cancer. The soluble VEGFR1 is overexpressed in placenta in preeclampsia patients. VEGFR2 has critical functions in physiological and pathologicalmore » angiogenesis through distinct signal transduction pathways regulating proliferation and migration of endothelial cells. VEGFR3, a receptor for the lymphatic growth factors VEGF-C and VEGF-D, but not for VEGF-A, regulates vascular and lymphatic endothelial cell function during embryogenesis. Loss-of-function variants of VEGFR3 have been identified in lymphedema. Formation of tumor lymphatics may be stimulated by tumor-produced VEGF-C, allowing increased spread of tumor metastases through the lymphatics. Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases.« less

  5. Influence of electrolytes on growth, phototropism, nutation and surface potential in etiolated cucumber seedlings

    NASA Technical Reports Server (NTRS)

    Spalding, E. P.; Cosgrove, D. J.

    1993-01-01

    A variety of electrolytes (10-30 mol m-3) increased the relative growth rate of etiolated cucumber (Cucumis sativus L. cv. Burpee's Pickler) hypocotyls by 20-50% relative to water-only controls. The nonelectrolyte mannitol inhibited growth by 10%. All salts tested were effective, regardless of chemical composition or valence. Measurements of cell-sap osmolality ruled out an osmotic mechanism for the growth stimulation by electrolytes. This, and the nonspecificity of the response, indicate that an electrical property of the solutions was responsible for their growth-stimulating activity. Measurements of surface electrical potential supported this reasoning. Treatment with electrolytes also enhanced nutation and altered the pattern of phototropic curvature development. A novel analytical method for quantitating these effects on growth was developed. The evidence indicates that electrolytes influence an electrophysiological parameter that is involved in the control of cell expansion and the coordination of growth underlying tropisms and nutations.

  6. Cellular context–mediated Akt dynamics regulates MAP kinase signaling thresholds during angiogenesis

    PubMed Central

    Hellesøy, Monica; Lorens, James B.

    2015-01-01

    The formation of new blood vessels by sprouting angiogenesis is tightly regulated by contextual cues that affect angiogeneic growth factor signaling. Both constitutive activation and loss of Akt kinase activity in endothelial cells impair angiogenesis, suggesting that Akt dynamics mediates contextual microenvironmental regulation. We explored the temporal regulation of Akt in endothelial cells during formation of capillary-like networks induced by cell–cell contact with vascular smooth muscle cells (vSMCs) and vSMC-associated VEGF. Expression of constitutively active Akt1 strongly inhibited network formation, whereas hemiphosphorylated Akt1 epi-alleles with reduced kinase activity had an intermediate inhibitory effect. Conversely, inhibition of Akt signaling did not affect endothelial cell migration or morphogenesis in vSMC cocultures that generate capillary-like structures. We found that endothelial Akt activity is transiently blocked by proteasomal degradation in the presence of SMCs during the initial phase of capillary-like structure formation. Suppressed Akt activity corresponded to the increased endothelial MAP kinase signaling that was required for angiogenic endothelial morphogenesis. These results reveal a regulatory principle by which cellular context regulates Akt protein dynamics, which determines MAP kinase signaling thresholds necessary drive a morphogenetic program during angiogenesis. PMID:26023089

  7. Regulators of G-protein signaling 4 in adrenal gland: localization, regulation, and role in aldosterone secretion.

    PubMed

    Romero, Damian G; Zhou, Ming Yi; Yanes, Licy L; Plonczynski, Maria W; Washington, Tanganika R; Gomez-Sanchez, Celso E; Gomez-Sanchez, Elise P

    2007-08-01

    Regulators of G-protein signaling (RGS proteins) interact with Galpha subunits of heterotrimeric G-proteins, accelerating the rate of GTP hydrolysis and finalizing the intracellular signaling triggered by the G-protein-coupled receptor (GPCR)-ligand interaction. Angiotensin II (Ang II) interacts with its GPCR in adrenal zona glomerulosa cells and triggers a cascade of intracellular signals that regulates steroidogenesis and proliferation. On screening for adrenal zona glomerulosa-specific genes, we found that RGS4 was exclusively localized in the zona glomerulosa of the rat adrenal cortex. We studied RGS4 expression and regulation in the rat adrenal gland, including the signaling pathways involved, as well as the role of RGS4 in steroidogenesis in human adrenocortical H295R cells. We reported that RGS4 mRNA expression in the rat adrenal gland was restricted to the adrenal zonal glomerulosa and upregulated by low-salt diet and Ang II infusion in rat adrenal glands in vivo. In H295R cells, Ang II caused a rapid and transient increase in RGS4 mRNA levels mediated by the calcium/calmodulin/calmodulin-dependent protein kinase and protein kinase C pathways. RGS4 overexpression by retroviral infection in H295R cells decreased Ang II-stimulated aldosterone secretion. In reporter assays, RGS4 decreased Ang II-mediated aldosterone synthase upregulation. In summary, RGS4 is an adrenal gland zona glomerulosa-specific gene that is upregulated by aldosterone secretagogues, in vivo and in vitro, and functions as a negative feedback of Ang II-triggered intracellular signaling. Alterations in RGS4 expression levels or functions may be involved in deregulations of Ang II signaling and abnormal aldosterone secretion.

  8. Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.

    PubMed

    Roberts, David D; Kaur, Sukhbir; Isenberg, Jeffrey S

    2017-10-20

    In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

  9. Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells.

    PubMed

    Nishida, Motohiro; Nishimura, Akiyuki; Matsunaga, Tetsuro; Motohashi, Hozumi; Kasamatsu, Shingo; Akaike, Takaaki

    2017-08-01

    Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

    PubMed Central

    Sharma, Ashish Ranjan; Seo, Eun-Min; Nam, Ju-Suk

    2015-01-01

    The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively. PMID:25945348

  11. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

    PubMed Central

    Stephen, Terri-Leigh; Higgs, Nathalie F.; Sheehan, David F.; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I. Lorena

    2015-01-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal

  12. Regulation of PCP by the Fat signaling pathway

    PubMed Central

    Matis, Maja; Axelrod, Jeffrey D.

    2013-01-01

    Planar cell polarity (PCP) in epithelia, orthogonal to the apical–basal axis, is essential for numerous developmental events and physiological functions. Drosophila model systems have been at the forefront of studies revealing insights into mechanisms regulating PCP and have revealed distinct signaling modules. One of these, involving the atypical cadherins Fat and Dachsous and the ectokinase Four-jointed, appears to link the direction of cell polarization to the tissue axes. We discuss models for the function of this signaling module as well as several unanswered questions that may guide future investigations. PMID:24142873

  13. ERK signaling pathway regulates sleep duration through activity-induced gene expression during wakefulness.

    PubMed

    Mikhail, Cyril; Vaucher, Angélique; Jimenez, Sonia; Tafti, Mehdi

    2017-01-24

    Wakefulness is accompanied by experience-dependent synaptic plasticity and an increase in activity-regulated gene transcription. Wake-induced genes are certainly markers of neuronal activity and may also directly regulate the duration of and need for sleep. We stimulated murine cortical cultures with the neuromodulatory signals that are known to control wakefulness in the brain and found that norepinephrine alone or a mixture of these neuromodulators induced activity-regulated gene transcription. Pharmacological inhibition of the various signaling pathways involved in the regulation of gene expression indicated that the extracellular signal-regulated kinase (ERK) pathway is the principal one mediating the effects of waking neuromodulators on gene expression. In mice, ERK phosphorylation in the cortex increased and decreased with wakefulness and sleep. Whole-body or cortical neuron-specific deletion of Erk1 or Erk2 significantly increased the duration of wakefulness in mice, and pharmacological inhibition of ERK phosphorylation decreased sleep duration and increased the duration of wakefulness bouts. Thus, this signaling pathway, which is highly conserved from Drosophila to mammals, is a key pathway that links waking experience-induced neuronal gene expression to sleep duration and quality. Copyright © 2017, American Association for the Advancement of Science.

  14. Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

    PubMed

    Schroeder, Elizabeth A; Shadel, Gerald S

    2014-01-01

    Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this response, we analyzed strains lacking the mitochondrial base-excision repair enzyme Ntg1p. Extension of CLS by mtROS signaling and reduced TORC1 activity, but not caloric restriction, was abrogated in ntg1Δ strains that exhibited mtDNA depletion without defects in respiration. The DNA damage response (DDR) kinase Rad53p, which transduces pro-longevity mtROS signals, is also activated in ntg1Δ strains. Restoring mtDNA copy number alleviated Rad53p activation and re-established CLS extension following mtROS signaling, indicating that Rad53p senses mtDNA depletion directly. Finally, DDR kinases regulate nucleus-mitochondria localization dynamics of Ntg1p. From these results, we conclude that the DDR pathway senses and may regulate Ntg1p-dependent mtDNA stability. Furthermore, Rad53p senses multiple mitochondrial stresses in a hierarchical manner to elicit specific physiological outcomes, exemplified by mtDNA depletion overriding the ability of Rad53p to transduce an adaptive mtROS longevity signal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Protein Tyrosine Phosphatases: From Housekeeping Enzymes to Master-Regulators of Signal Transduction

    PubMed Central

    Tonks, Nicholas K.

    2013-01-01

    There are many misconceptions surrounding the roles of protein phosphatases in the regulation of signal transduction, perhaps the most damaging of which is the erroneous view that these enzymes exert their effects merely as constitutively active housekeeping enzymes. On the contrary, the phosphatases are critical, specific regulators of signaling in their own right and serve an essential function, in a coordinated manner with the kinases, to determine the response to a physiological stimulus. This review is a personal perspective on the development of our understanding of the protein tyrosine phosphatase (PTP) family of enzymes. I have discussed various aspects of the structure, regulation and function of the PTP family, which I hope will illustrate the fundamental importance of these enzymes to the control of signal transduction. PMID:23176256

  16. Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding.

    PubMed

    Jung, Seung-Ryoung; Kushmerick, Christopher; Seo, Jong Bae; Koh, Duk-Su; Hille, Bertil

    2017-07-11

    Binding of agonists to G-protein-coupled receptors (GPCRs) activates heterotrimeric G proteins and downstream signaling. Agonist-bound GPCRs are then phosphorylated by protein kinases and bound by arrestin to trigger desensitization and endocytosis. Arrestin plays another important signaling function. It recruits and regulates activity of an extracellular signal-regulated kinase (ERK) cascade. However, molecular details and timing of ERK activation remain fundamental unanswered questions that limit understanding of how arrestin-dependent GPCR signaling controls cell functions. Here we validate and model a system that tracks the dynamics of interactions of arrestin with receptors and of ERK activation using optical reporters. Our intermolecular FRET measurements in living cells are consistent with β-arrestin binding to M 1 muscarinic acetylcholine receptors (M 1 Rs) in two different binding modes, transient and stable. The stable mode persists for minutes after agonist removal. The choice of mode is governed by phosphorylation on key residues in the third intracellular loop of the receptor. We detect a similar intramolecular conformational change in arrestin in either binding mode. It develops within seconds of arrestin binding to the M 1 receptor, and it reverses within seconds of arrestin unbinding from the transient binding mode. Furthermore, we observed that, when stably bound to phosphorylated M 1 R, β-arrestin scaffolds and activates MEK-dependent ERK. In contrast, when transiently bound, β-arrestin reduces ERK activity via recruitment of a protein phosphatase. All this ERK signaling develops at the plasma membrane. In this scaffolding hypothesis, a shifting balance between the two arrestin binding modes determines the degree of ERK activation at the membrane.

  17. Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding

    PubMed Central

    Jung, Seung-Ryoung; Kushmerick, Christopher; Seo, Jong Bae; Koh, Duk-Su

    2017-01-01

    Binding of agonists to G-protein–coupled receptors (GPCRs) activates heterotrimeric G proteins and downstream signaling. Agonist-bound GPCRs are then phosphorylated by protein kinases and bound by arrestin to trigger desensitization and endocytosis. Arrestin plays another important signaling function. It recruits and regulates activity of an extracellular signal-regulated kinase (ERK) cascade. However, molecular details and timing of ERK activation remain fundamental unanswered questions that limit understanding of how arrestin-dependent GPCR signaling controls cell functions. Here we validate and model a system that tracks the dynamics of interactions of arrestin with receptors and of ERK activation using optical reporters. Our intermolecular FRET measurements in living cells are consistent with β-arrestin binding to M1 muscarinic acetylcholine receptors (M1Rs) in two different binding modes, transient and stable. The stable mode persists for minutes after agonist removal. The choice of mode is governed by phosphorylation on key residues in the third intracellular loop of the receptor. We detect a similar intramolecular conformational change in arrestin in either binding mode. It develops within seconds of arrestin binding to the M1 receptor, and it reverses within seconds of arrestin unbinding from the transient binding mode. Furthermore, we observed that, when stably bound to phosphorylated M1R, β-arrestin scaffolds and activates MEK-dependent ERK. In contrast, when transiently bound, β-arrestin reduces ERK activity via recruitment of a protein phosphatase. All this ERK signaling develops at the plasma membrane. In this scaffolding hypothesis, a shifting balance between the two arrestin binding modes determines the degree of ERK activation at the membrane. PMID:28652372

  18. Nutrient Regulation of the mTOR Complex 1 Signaling Pathway

    PubMed Central

    Kim, Sang Gyun; Buel, Gwen R.; Blenis, John

    2013-01-01

    The mammalian target of rapamycin (mTOR) is an evolutionally conserved kinase which exists in two distinct structural and functional complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Of the two complexes, mTORC1 couples nutrient abundance to cell growth and proliferation by sensing and integrating a variety of inputs arising from amino acids, cellular stresses, energy status, and growth factors. Defects in mTORC1 regulation are implicated in the development of many metabolic diseases, including cancer and diabetes. Over the past decade, significant advances have been made in deciphering the complexity of the signaling processes contributing to mTORC1 regulation and function, but the mechanistic details are still not fully understood. In particular, how amino acid availability is sensed by cells and signals to mTORC1 remains unclear. In this review, we discuss the current understanding of nutrient-dependent control of mTORC1 signaling and will focus on the key components involved in amino acid signaling to mTORC1. PMID:23694989

  19. Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

    PubMed

    Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

    2006-06-01

    Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

  20. Atypical regulators of Wnt/β-catenin signaling as potential therapeutic targets in Hepatocellular Carcinoma.

    PubMed

    Chen, Jianxiang; Rajasekaran, Muthukumar; Hui, Kam M

    2017-06-01

    Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma. Therefore, besides mutations in the canonical Wnt components, there must be additional atypical regulation or regulators during Wnt signaling activation that promote liver carcinogenesis. In this mini-review, we have tried to summarize some of these well-established factors and to highlight some recently identified novel factors in the Wnt/β-catenin signaling pathway in hepatocellular carcinoma. Impact statement Early recurrence of human hepatocellular carcinoma (HCC) is a frequent cause of poor survival after potentially curative liver resection. Among the deregulated signaling cascades in HCC, evidence indicates that alterations in the Wnt/β-catenin signaling pathway play key roles in hepatocarcinogenesis. In this review, we summarize the potential molecular mechanisms how the microtubule-associated Protein regulator of cytokinesis 1 (PRC1), a direct Wnt signaling target previously identified in our laboratory to be up-regulated in HCC, in promoting cancer proliferation, stemness, metastasis and tumorigenesis through a complex regulatory circuitry of Wnt3a activities.

  1. Mechanosensitive β-catenin signaling regulates lymphatic vascular development

    PubMed Central

    Cha, Boksik; Srinivasan, R. Sathish

    2016-01-01

    The Wnt/β-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/β-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/β-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). β-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of β-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/β-catenin signaling is a mechanotransducer that links fluid force with lymphatic vascular development. [BMB Reports 2016; 49(8): 403-404] PMID:27418286

  2. Biophysical mechanism of transient retinal phototropism in rod photoreceptors.

    PubMed

    Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Gai, Shaoyan; Yao, Xincheng

    2016-02-13

    Oblique light stimulation evoked transient retinal phototropism (TRP) has been recently detected in frog and mouse retinas. High resolution microscopy of freshly isolated retinas indicated that the TRP is predominated by rod photoreceptors. Comparative confocal microscopy and optical coherence tomography (OCT) revealed that the TRP predominantly occurred from the photoreceptor outer segment (OS). However, biophysical mechanism of rod OS change is still unknown. In this study, frog retinal slices, which open a cross section of retinal photoreceptor and other functional layers, were used to test the effect of light stimulation on rod OS. Near infrared light microscopy was employed to monitor photoreceptor changes in retinal slices stimulated by a rectangular-shaped visible light flash. Rapid rod OS length change was observed after the stimulation delivery. The magnitude and direction of the rod OS change varied with the position of the rods within the stimulated area. In the center of stimulated region the length of the rod OS shrunk, while in the peripheral region the rod OS tip swung towards center region in the plane perpendicular to the incident stimulus light. Our experimental result and theoretical analysis suggest that the observed TRP may reflect unbalanced disc-shape change due to localized pigment bleaching. Further investigation is required to understand biochemical mechanism of the observed rod OS kinetics. Better study of the TRP may provide a noninvasive biomarker to enable early detection of age-related macular degeneration (AMD) and other diseases that are known to produce retinal photoreceptor dysfunctions.

  3. Biophysical mechanism of transient retinal phototropism in rod photoreceptors

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Gai, Shaoyan; Yao, Xincheng

    2016-03-01

    Oblique light stimulation evoked transient retinal phototropism (TRP) has been recently detected in frog and mouse retinas. High resolution microscopy of freshly isolated retinas indicated that the TRP is predominated by rod photoreceptors. Comparative confocal microscopy and optical coherence tomography (OCT) revealed that the TRP predominantly occurred from the photoreceptor outer segment (OS). However, biophysical mechanism of rod OS change is still unknown. In this study, frog retinal slices, which open a cross section of retinal photoreceptor and other functional layers, were used to test the effect of light stimulation on rod OS. Near infrared light microscopy was employed to monitor photoreceptor changes in retinal slices stimulated by a rectangular-shaped visible light flash. Rapid rod OS length change was observed after the stimulation delivery. The magnitude and direction of the rod OS change varied with the position of the rods within the stimulated area. In the center of stimulated region the length of the rod OS shrunk, while in the peripheral region the rod OS tip swung towards center region in the plane perpendicular to the incident stimulus light. Our experimental result and theoretical analysis suggest that the observed TRP may reflect unbalanced disc-shape change due to localized pigment bleaching. Further investigation is required to understand biochemical mechanism of the observed rod OS kinetics. Better study of the TRP may provide a noninvasive biomarker to enable early detection of age-related macular degeneration (AMD) and other diseases that are known to produce retinal photoreceptor dysfunctions.

  4. Sprouty2 regulates endochondral bone formation by modulation of RTK and BMP signaling

    PubMed Central

    Joo, Adriane; Long, Roger; Cheng, Zhiqiang; Alexander, Courtney; Chang, Wenhan; Klein, Ophir D.

    2016-01-01

    Skeletal development is regulated by the coordinated activity of signaling molecules that are both produced locally by cartilage and bone cells and also circulate systemically. During embryonic development and postnatal bone remodeling, receptor tyrosine kinase (RTK) superfamily members play critical roles in the proliferation, survival, and differentiation of chondrocytes, osteoblasts, osteoclasts, and other bone cells. Recently, several molecules that regulate RTK signaling have been identified, including the four members of the Sprouty (Spry) family (Spry1–4). We report that Spry2 plays an important role in regulation of endochondral bone formation. Mice in which the Spry2 gene has been deleted have defective chondrogenesis and endochondral bone formation, with a postnatal decrease in skeletal size and trabecular bone mass. In these constitutive Spry2 mutants, both chondrocytes and osteoblasts undergo increased cell proliferation and impaired terminal differentiation. Tissue-specific Spry2 deletion by either osteoblast- (Col1-Cre) or chondrocyte- (Col2-Cre) specific drivers led to decreased relative bone mass, demonstrating the critical role of Spry2 in both cell types. Molecular analyses of signaling pathways in Spry2−/− mice revealed an unexpected upregulation of BMP signaling and decrease in RTK signaling. These results identify Spry2 as a critical regulator of endochondral bone formation that modulates signaling in both osteoblast and chondrocyte lineages. PMID:27130872

  5. Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

    PubMed Central

    Kaur, Sukhbir

    2017-01-01

    Abstract Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H2S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H2S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874–911. PMID:28712304

  6. Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway in depressive disorder☆

    PubMed Central

    Wang, Hongyan; Zhang, Yingquan; Qiao, Mingqi

    2013-01-01

    The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression. PMID:25206732

  7. Global regulation by the seven-component Pi signaling system.

    PubMed

    Hsieh, Yi-Ju; Wanner, Barry L

    2010-04-01

    This review concerns how Escherichia coli detects environmental inorganic orthophosphate (P(i)) to regulate genes of the phosphate (Pho) regulon by the PhoR/PhoB two-component system (TCS). P(i) control by the PhoR/PhoB TCS is a paradigm of a bacterial signal transduction pathway in which occupancy of a cell surface receptor(s) controls gene expression in the cytoplasm. The P(i) signaling pathway requires seven proteins, all of which probably interact in a membrane-associated signaling complex. Our latest studies show that P(i) signaling involves three distinct processes, which appear to correspond to different states of the sensory histidine kinase PhoR: an inhibition state, an activation state, and a deactivation state. We describe a revised model for P(i) signal transduction of the E. coli Pho regulon. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Arabidopsis ROP-interactive CRIB motif-containing protein 1 (RIC1) positively regulates auxin signalling and negatively regulates abscisic acid (ABA) signalling during root development.

    PubMed

    Choi, Yunjung; Lee, Yuree; Kim, Soo Young; Lee, Youngsook; Hwang, Jae-Ung

    2013-05-01

    Auxin and abscisic acid (ABA) modulate numerous aspects of plant development together, mostly in opposite directions, suggesting that extensive crosstalk occurs between the signalling pathways of the two hormones. However, little is known about the nature of this crosstalk. We demonstrate that ROP-interactive CRIB motif-containing protein 1 (RIC1) is involved in the interaction between auxin- and ABA-regulated root growth and lateral root formation. RIC1 expression is highly induced by both hormones, and expressed in the roots of young seedlings. Whereas auxin-responsive gene induction and the effect of auxin on root growth and lateral root formation were suppressed in the ric1 knockout, ABA-responsive gene induction and the effect of ABA on seed germination, root growth and lateral root formation were potentiated. Thus, RIC1 positively regulates auxin responses, but negatively regulates ABA responses. Together, our results suggest that RIC1 is a component of the intricate signalling network that underlies auxin and ABA crosstalk. © 2012 Blackwell Publishing Ltd.

  9. Regulation of Strigolactone Biosynthesis by Gibberellin Signaling.

    PubMed

    Ito, Shinsaku; Yamagami, Daichi; Umehara, Mikihisa; Hanada, Atsushi; Yoshida, Satoko; Sasaki, Yasuyuki; Yajima, Shunsuke; Kyozuka, Junko; Ueguchi-Tanaka, Miyako; Matsuoka, Makoto; Shirasu, Ken; Yamaguchi, Shinjiro; Asami, Tadao

    2017-06-01

    Strigolactones (SLs) are a class of plant hormones that regulate diverse physiological processes, including shoot branching and root development. They also act as rhizosphere signaling molecules to stimulate the germination of root parasitic weeds and the branching of arbuscular mycorrhizal fungi. Although various types of cross talk between SLs and other hormones have been reported in physiological analyses, the cross talk between gibberellin (GA) and SLs is poorly understood. We screened for chemicals that regulate the level of SLs in rice ( Oryza sativa ) and identified GA as, to our knowledge, a novel SL-regulating molecule. The regulation of SL biosynthesis by GA is dependent on the GA receptor GID1 and F-box protein GID2. GA treatment also reduced the infection of rice plants by the parasitic plant witchers weed ( Striga hermonthica ). These data not only demonstrate, to our knowledge, the novel plant hormone cross talk between SL and GA, but also suggest that GA can be used to control parasitic weed infections. © 2017 American Society of Plant Biologists. All Rights Reserved.

  10. Signaling, Regulation, and Specificity of the Type II p21-activated Kinases.

    PubMed

    Ha, Byung Hak; Morse, Elizabeth M; Turk, Benjamin E; Boggon, Titus J

    2015-05-22

    The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Cullin-4 regulates Wingless and JNK signaling-mediated cell death in the Drosophila eye

    PubMed Central

    Tare, Meghana; Sarkar, Ankita; Bedi, Shimpi; Kango-Singh, Madhuri; Singh, Amit

    2016-01-01

    In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood. In a gain-of-function screen, we found that misexpression of cullin-4 (cul-4), an ubiquitin ligase, can rescue reduced eye mutant phenotypes. Previously, cul-4 has been shown to regulate chromatin remodeling, cell cycle and cell division. Genetic characterization of cul-4 in the developing eye revealed that loss-of-function of cul-4 exhibits a reduced eye phenotype. Analysis of twin-spots showed that in comparison with their wild-type counterparts, the cul-4 loss-of-function clones fail to survive. Here we show that cul-4 clones are eliminated by induction of cell death due to activation of caspases. Aberrant activation of signaling pathways is known to trigger cell death in the developing eye. We found that Wingless (Wg) and c-Jun-amino-terminal-(NH2)-Kinase (JNK) signaling are ectopically induced in cul-4 mutant clones, and these signals co-localize with the dying cells. Modulating levels of Wg and JNK signaling by using agonists and antagonists of these pathways demonstrated that activation of Wg and JNK signaling enhances cul-4 mutant phenotype, whereas downregulation of Wg and JNK signaling rescues the cul-4 mutant phenotypes of reduced eye. Here we present evidences to demonstrate that cul-4 is involved in restricting Wg signaling and downregulation of JNK signaling-mediated cell death during early eye development. Overall, our studies provide insights into a novel role of cul-4 in promoting cell

  12. Auxins and tropisms

    NASA Technical Reports Server (NTRS)

    Muday, G. K.; Brown, C. S. (Principal Investigator)

    2001-01-01

    Differential growth of plants in response to the changes in the light and gravity vectors requires a complex signal transduction cascade. Although many of the details of the mechanisms by which these differential growth responses are induced are as yet unknown, auxin has been implicated in both gravitropism and phototropism. Specifically, the redistribution of auxin across gravity or light-stimulated tissues has been detected and shown to be required for this process. The approaches by which auxin has been implicated in tropisms include isolation of mutants altered in auxin transport or response with altered gravitropic or phototropic response, identification of auxin gradients with radiolabeled auxin and auxin-inducible gene reporter systems, and by use of inhibitors of auxin transport that block gravitropism and phototropism. Proteins that transport auxin have been identified and the mechanisms which determine auxin transport polarity have been explored. In addition, recent evidence that reversible protein phosphorylation controls this process is summarized. Finally, the data in support of several hypotheses for mechanisms by which auxin transport could be differentially regulated during gravitropism are examined. Although many details of the mechanisms by which plants respond to gravity and light are not yet clear, numerous recent studies demonstrate the role of auxin in these processes.

  13. The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development.

    PubMed

    Kazanskaya, Olga; Ohkawara, Bisei; Heroult, Melanie; Wu, Wei; Maltry, Nicole; Augustin, Hellmut G; Niehrs, Christof

    2008-11-01

    The vertebrate embryonic vasculature develops from angioblasts, which are specified from mesodermal precursors and develop in close association with blood cells. The signals that regulate embryonic vasculogenesis and angiogenesis are incompletely understood. Here, we show that R-spondin 3 (Rspo3), a member of a novel family of secreted proteins in vertebrates that activate Wnt/beta-catenin signaling, plays a key role in these processes. In Xenopus embryos, morpholino antisense knockdown of Rspo3 induces vascular defects because Rspo3 is essential for regulating the balance between angioblast and blood cell specification. In mice, targeted disruption of Rspo3 leads to embryonic lethality caused by vascular defects. Specifically in the placenta, remodeling of the vascular plexus is impaired. In human endothelial cells, R-spondin signaling promotes proliferation and sprouting angiogenesis in vitro, indicating that Rspo3 can regulate endothelial cells directly. We show that vascular endothelial growth factor is an immediate early response gene and a mediator of R-spondin signaling. The results identify Rspo3 as a novel, evolutionarily conserved angiogenic factor in embryogenesis.

  14. Mechanism regulating nuclear calcium signaling.

    PubMed

    Malviya, Anant N; Klein, Christian

    2006-01-01

    Although the outer nuclear membrane is continuous with the endoplasmic reticulum, it is possible to isolate nuclei both intact and free from endoplasmic reticulum contaminants. The outer and the inner nuclear membranes can be purified free from cross-contamination. Evidence in support of autonomous regulation of nuclear calcium signaling relies upon the investigations with isolated nuclei. Mechanisms for generating calcium signaling in the nucleus have been identified. Two calcium transporting systems, an ATP-dependant nuclear Ca(2+)-ATPase and an IP4-mediated inositol 1,3,4,5-tetrakisphosphate receptor, are located on the outer nuclear membrane. Thus, ATP and IP4, depending on external free calcium concentrations, are responsible for filling the nuclear envelope calcium pool. The inositol 1,4,5-trisphosphate receptor is located on the inner nuclear membrane with its ligand binding domain facing toward the nucleoplasm. Likewise, the ryanodine receptor is located on the inner nuclear membrane and its ligand cADP-ribose is generated within the nucleus. A 120 kDa protein fragment of nuclear PLC-gamma1 is stimulated in vivo by epidermal growth factor nuclear signaling coincident with the time course of nuclear membrane epidermal growth factor receptor activation. Stimulated 120 kDa protein fragment interacts with PIKE, a nuclear GTPase, and together they form a complex with PI[3]kinase serving as a module for nuclear PI[3]K stimulation. Thus, the nucleus has its own IP(3) generating system.

  15. Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development

    PubMed Central

    Kohn, Anat; Dong, Yufeng; Mirando, Anthony J.; Jesse, Alana M.; Honjo, Tasuku; Zuscik, Michael J.; O’Keefe, Regis J.; Hilton, Matthew J.

    2012-01-01

    The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination of Notch signaling specifically within developing and committed chondrocytes, or a determination of whether cartilage and bone formation are regulated via RBPjκ-dependent or -independent Notch signaling mechanisms. To develop a complete understanding of Notch signaling during cartilage and bone development we generated and compared general Notch gain-of-function (Rosa-NICDf/+), RBPjκ-deficient (Rbpjκf/f), and RBPjκ-deficient Notch gain-of-function (Rosa-NICDf/+;Rbpjκf/f) conditional mutant mice, where activation or deletion of floxed alleles were specifically targeted to mesenchymal progenitors (Prx1Cre) or committed chondrocytes (inducible Col2CreERT2). These data demonstrate, for the first time, that Notch regulation of chondrocyte maturation is solely mediated via the RBPjκ-dependent pathway, and that the perichodrium or osteogenic lineage probably influences chondrocyte terminal maturation and turnover of the cartilage matrix. Our study further identifies the cartilage-specific RBPjκ-independent pathway as crucial for the proper regulation of chondrocyte proliferation, survival and columnar chondrocyte organization. Unexpectedly, the RBPjκ-independent Notch pathway was also identified as an important long-range cell non-autonomous regulator of perichondral bone formation and an important cartilage-derived signal required for coordinating chondrocyte and osteoblast differentiation during endochondral bone development. Finally, cartilage-specific RBPjκ-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development. PMID:22354840

  16. Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

    PubMed Central

    Park, Sangbin; Bustamante, Erika L.; Antonova, Julie; McLean, Graeme W.; Kim, Seung K.

    2011-01-01

    Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism. PMID:21901108

  17. [Extracellular signal-regulated kinase signaling pathway regulates the endothelial differentiation of periodontal ligament stem cells].

    PubMed

    Zhu, Hong; Luo, Lankun; Wang, Ying; Tan, Jun; Xue, Peng; Wang, Qintao

    2016-03-01

    To investigate the effect of extracellular signal-regulated kinase (ERK) signaling pathway on the endothelial differentiation of periodontal ligament stem cells (PDLSC). Human PDLSC was cultured in the medium with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) to induce endothelial differentiation. Endothelial inducing cells was incubated with U0126, a specific p-ERK1/2 inhibitor. PDLSC from one person were randomly divided into four groups: control group, endothelial induced group, endothelial induced+DMSO group and endothelial induced+U0126 group. The protein expression of the p-EKR1/2 was analyzed by Western blotting at 0, 1, 3, 6 and 12 hours during endonthelial induction. The mRNA expressions of CD31, VE-cadherin, and VEGF were detected by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) after a 7-day induction. The proportion of CD31(+) to VE-cadherin(+) cells was identified by flow cytometry, and the ability of capillary-like tubes formation was detected by Matrigel assay after a 14-day induction. The measurement data were statistically analyzed. Phosphorylated ERK1/2 protein level in PDLSC was increased to 1.24±0.12 and 1.03±0.24 at 1 h and 3 h respectively, during the endothelial induction (P<0.01). The mRNA expressions of CD31 and VEGF in induced+U0126 group were decreased to 0.09±0.18 and 0.49±0.17, which were both significantly different with those in induced group (P<0.05). The proportion of CD31(+) to VE-cadherin(+) cells of induced+U0126 group were decreased to 5.22±0.85 and 3.56±0.87, which were both significantly different with those in induced group (P<0.05). In Matrigel assay, the branching points, tube number and tube length were decreased to 7.0±2.7, 33.5±6.4, and (15 951.0±758.1) pixels, which were all significantly different with those in induced group (P<0.05). The endothelial differentiation of PDLSC is positively regulated by ERK signaling pathway. Inhibition of

  18. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals.

    PubMed

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2017-07-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.

  19. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

    PubMed Central

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2018-01-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

  20. Analysis of multiple photoreceptor pigments for phototropism in a mutant of Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Konjevic, R.; Khurana, J. P.; Poff, K. L.

    1992-01-01

    The shape of the fluence-response relationship for the phototropic response of the JK224 strain of Arabidopsis thaliana depends on the fluence rate and wavelength of the actinic light. At low fluence rate (0.1 micromole m-2 s-1), the response to 450-nm light is characterized by a single maximum at about 9 micromoles m-2. At higher fluence rate (0.4 micromole m-2 s-1), the response shows two maxima, at 4.5 and 9 micromoles m-2. The response to 510-nm light shows a single maximum at 4.5 micromoles m-2. Unilateral preirradiation with high fluence rate (25 micromoles m-2 s-1) 510-nm light eliminates the maximum at 4.5 micromoles m-2 in the fluence response curve to a subsequent unilateral 450-nm irradiation, while the second maximum at 9 micromoles m-2 is unaffected. Based on these results, it is concluded that a single photoreceptor pigment has been altered in the JK224 strain of Arabidopsis thaliana.

  1. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

    PubMed

    Ray, Poulomi; Chapman, Susan C

    2015-01-01

    Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP) and Transforming Growth Factor beta (TGF-β) signaling pathways. Rho Kinase (ROCK)-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

  2. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling

    PubMed Central

    Ray, Poulomi; Chapman, Susan C.

    2015-01-01

    Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP) and Transforming Growth Factor beta (TGF-β) signaling pathways. Rho Kinase (ROCK)-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis. PMID:26237312

  3. An Integrated Phosphoproteomics Work Flow Reveals Extensive Network Regulation in Early Lysophosphatidic Acid Signaling*

    PubMed Central

    Schreiber, Thiemo B.; Mäusbacher, Nina; Kéri, György; Cox, Jürgen; Daub, Henrik

    2010-01-01

    Lysophosphatidic acid (LPA) induces a variety of cellular signaling pathways through the activation of its cognate G protein-coupled receptors. To investigate early LPA responses and assess the contribution of epidermal growth factor (EGF) receptor transactivation in LPA signaling, we performed phosphoproteomics analyses of both total cell lysate and protein kinase-enriched fractions as complementary strategies to monitor phosphorylation changes in A498 kidney carcinoma cells. Our integrated work flow enabled the identification and quantification of more than 5,300 phosphorylation sites of which 224 were consistently regulated by LPA. In addition to induced phosphorylation events, we also obtained evidence for early dephosphorylation reactions due to rapid phosphatase regulation upon LPA treatment. Phosphorylation changes induced by direct heparin-binding EGF-like growth factor-mediated EGF receptor activation were typically weaker and only detected on a subset of LPA-regulated sites, indicating signal integration among EGF receptor transactivation and other LPA-triggered pathways. Our results reveal rapid phosphoregulation of many proteins not yet implicated in G protein-coupled receptor signaling and point to various additional mechanisms by which LPA might regulate cell survival and migration as well as gene transcription on the molecular level. Moreover, our phosphoproteomics analysis of both total lysate and kinase-enriched fractions provided highly complementary parts of the LPA-regulated signaling network and thus represents a useful and generic strategy toward comprehensive signaling studies on a system-wide level. PMID:20071362

  4. SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking.

    PubMed

    Dragone, Leonard L; Shaw, Laura A; Myers, Margaret D; Weiss, Arthur

    2009-11-01

    Src-like adapter proteins (SLAP and SLAP-2) constitute a family of proteins that are expressed in a variety of cell types but are studied most extensively in lymphocytes. They have been shown to associate with proximal components of the T-cell receptor (TCR) and B-cell receptor (BCR) signaling complexes. An interaction of SLAP with c-Cbl leads to the ubiquitination and degradation of phosphorylated components of the TCR- and BCR-signaling complexes. The absence of this process in immature SLAP-deficient T and B cells leads to increased immunoreceptor levels due to decreased intracellular retention and degradation. We propose a model in which SLAP-dependent regulation of immunoreceptor levels allows for finer control of immunoreceptor signaling. Thus, SLAP functions to dampen immunoreceptor signaling, thereby influencing lymphocyte development and repertoire selection.

  5. Light and gravity signals synergize in modulating plant development

    PubMed Central

    Vandenbrink, Joshua P.; Kiss, John Z.; Herranz, Raul; Medina, F. Javier

    2014-01-01

    Tropisms are growth-mediated plant movements that help plants to respond to changes in environmental stimuli. The availability of water and light, as well as the presence of a constant gravity vector, are all environmental stimuli that plants sense and respond to via directed growth movements (tropisms). The plant response to gravity (gravitropism) and the response to unidirectional light (phototropism) have long been shown to be interconnected growth phenomena. Here, we discuss the similarities in these two processes, as well as the known molecular mechanisms behind the tropistic responses. We also highlight research done in a microgravity environment in order to decouple two tropisms through experiments carried out in the absence of a significant unilateral gravity vector. In addition, alteration of gravity, especially the microgravity environment, and light irradiation produce important effects on meristematic cells, the undifferentiated, highly proliferating, totipotent cells which sustain plant development. Microgravity produces the disruption of meristematic competence, i.e., the decoupling of cell proliferation and cell growth, affecting the regulation of the cell cycle and ribosome biogenesis. Light irradiation, especially red light, mediated by phytochromes, has an activating effect on these processes. Phytohormones, particularly auxin, also are key mediators in these alterations. Upcoming experiments on the International Space Station will clarify some of the mechanisms and molecular players of the plant responses to these environmental signals involved in tropisms and the cell cycle. PMID:25389428

  6. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    PubMed

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  7. Tgf-beta induced Erk phosphorylation of smad linker region regulates smad signaling.

    PubMed

    Hough, Chris; Radu, Maria; Doré, Jules J E

    2012-01-01

    The Transforming Growth Factor-Beta (TGF-β) family is involved in regulating a variety of cellular processes such as apoptosis, differentiation, and proliferation. TGF-β binding to a Serine/Threonine kinase receptor complex causes the recruitment and subsequent activation of transcription factors known as smad2 and smad3. These proteins subsequently translocate into the nucleus to negatively or positively regulate gene expression. In this study, we define a second signaling pathway leading to TGF-β receptor activation of Extracellular Signal Regulated Kinase (Erk) in a cell-type dependent manner. TGF-β induced Erk activation was found in phenotypically normal mesenchymal cells, but not normal epithelial cells. By activating phosphotidylinositol 3-kinase (PI3K), TGF-β stimulates p21-activated kinase2 (Pak2) to phosphorylate c-Raf, ultimately resulting in Erk activation. Activation of Erk was necessary for TGF-β induced fibroblast replication. In addition, Erk phosphorylated the linker region of nuclear localized smads, resulting in increased half-life of C-terminal phospho-smad 2 and 3 and increased duration of smad target gene transcription. Together, these data show that in mesenchymal cell types the TGF-β/PI3K/Pak2/Raf/MEK/Erk pathway regulates smad signaling, is critical for TGF-β-induced growth and is part of an integrated signaling web containing multiple interacting pathways rather than discrete smad/non-smad pathways.

  8. VEGFR-3 signaling is regulated by a G-protein activator, activator of G-protein signaling 8, in lymphatic endothelial cells.

    PubMed

    Sakima, Miho; Hayashi, Hisaki; Mamun, Abdullah Al; Sato, Motohiko

    2018-07-01

    Vascular endothelial growth factor C (VEGFC) and its cognate receptor VEGFR-3 play a key role in lymphangiogenesis. We previously reported that an ischemia-inducible Gβγ signal regulator, activator of G-protein signaling 8 (AGS8), regulated the subcellular distribution of vascular endothelial growth factor receptor-2 (VEGFR-2) and influenced VEGFA-induced signaling in vascular endothelial cells. Here, we report that AGS8 regulates VEGFR-3, which is another subtype of the VEGF receptor family, and mediates VEGFC signaling in human dermal lymphatic endothelial cells (HDLECs). VEGFC stimulated the proliferation of HDLECs and tube formation by HDLECs, which were inhibited by knocking down AGS8 by small interfering RNA (siRNA). AGS8 siRNA inhibited VEGFC-mediated phosphorylation of VEGFR-3 and its downstream molecules, including ERK1/2 and AKT. Analysis of fluorescence-activated cell sorting and immunofluorescence staining demonstrated that AGS8 knockdown was associated with a reduction of VEGFR-3 at the cell surface. Endocytosis inhibitors did not rescue the decrease of cell-surface VEGFR-3, suggesting that AGS8 regulated the trafficking of VEGFR-3 to the plasma membrane. An immunoprecipitation assay indicated that VEGFR-3 formed a complex including AGS8 and Gβγ in cells. These data suggest the novel regulation of VEGFC-VEGFR-3 by AGS8 in HDLECs and a potential role for AGS8 in lymphangiogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling.

    PubMed

    Noctor, Graham; Foyer, Christine H

    2016-07-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. © 2016 American Society of Plant Biologists. All Rights Reserved.

  10. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    PubMed Central

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  11. Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk

    PubMed Central

    Oladimeji, Peter; Cui, Hongmei; Zhang, Chen; Chen, Taosheng

    2016-01-01

    Introduction Protein-protein interaction and signaling crosstalk contribute to the regulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and broaden their cellular function. Area covered This review covers key historic discoveries and recent advances in our understanding of the broad function of PXR and CAR and their regulation by protein-protein interaction and signaling crosstalk. Expert opinion PXR and CAR were first discovered as xenobiotic receptors. However, it is clear that PXR and CAR perform a much broader range of cellular functions through protein-protein interaction and signaling crosstalk, which typically mutually affect the function of all the partners involved. Future research on PXR and CAR should, therefore, look beyond their xenobiotic function. PMID:27295009

  12. TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

    PubMed Central

    Rahman, Md Shaifur; Akhtar, Naznin; Jamil, Hossen Mohammad; Banik, Rajat Suvra; Asaduzzaman, Sikder M

    2015-01-01

    Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics. PMID:26273537

  13. Caveolin-1 regulates shear stress-dependent activation of extracellular signal-regulated kinase

    NASA Technical Reports Server (NTRS)

    Park, H.; Go, Y. M.; Darji, R.; Choi, J. W.; Lisanti, M. P.; Maland, M. C.; Jo, H.

    2000-01-01

    Fluid shear stress activates a member of the mitogen-activated protein (MAP) kinase family, extracellular signal-regulated kinase (ERK), by mechanisms dependent on cholesterol in the plasma membrane in bovine aortic endothelial cells (BAEC). Caveolae are microdomains of the plasma membrane that are enriched with cholesterol, caveolin, and signaling molecules. We hypothesized that caveolin-1 regulates shear activation of ERK. Because caveolin-1 is not exposed to the outside, cells were minimally permeabilized by Triton X-100 (0.01%) to deliver a neutralizing, polyclonal caveolin-1 antibody (pCav-1) inside the cells. pCav-1 then bound to caveolin-1 and inhibited shear activation of ERK but not c-Jun NH(2)-terminal kinase. Epitope mapping studies showed that pCav-1 binds to caveolin-1 at two regions (residues 1-21 and 61-101). When the recombinant proteins containing the epitopes fused to glutathione-S-transferase (GST-Cav(1-21) or GST-Cav(61-101)) were preincubated with pCav-1, only GST-Cav(61-101) reversed the inhibitory effect of the antibody on shear activation of ERK. Other antibodies, including m2234, which binds to caveolin-1 residues 1-21, had no effect on shear activation of ERK. Caveolin-1 residues 61-101 contain the scaffolding and oligomerization domains, suggesting that binding of pCav-1 to these regions likely disrupts the clustering of caveolin-1 or its interaction with signaling molecules involved in the shear-sensitive ERK pathway. We suggest that caveolae-like domains play a critical role in the mechanosensing and/or mechanosignal transduction of the ERK pathway.

  14. Tangeretin inhibits extracellular-signal-regulated kinase (ERK) phosphorylation.

    PubMed

    Van Slambrouck, Séverine; Parmar, Virinder S; Sharma, Sunil K; De Bondt, Bart; Foré, Fleur; Coopman, Peter; Vanhoecke, Barbara W; Boterberg, Tom; Depypere, Herman T; Leclercq, Guy; Bracke, Marc E

    2005-03-14

    Tangeretin is a methoxyflavone from citrus fruits, which inhibits growth of human mammary cancer cells and cytolysis by natural killer cells. Attempting to unravel the flavonoid's action mechanism, we found that it inhibited extracellular-signal-regulated kinases 1/2 (ERK1/2) phosphorylation in a dose- and time-dependent way. In human T47D mammary cancer cells this inhibition was optimally observed after priming with estradiol. The spectrum of the intracellular signalling kinase inhibition was narrow and comparison of structural congeners showed that inhibition of ERK phosphorylation was not unique for tangeretin. Our data add tangeretin to the list of small kinase inhibitors with a restricted intracellular inhibition profile.

  15. Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

    PubMed Central

    Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

    2015-01-01

    The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

  16. Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling.

    PubMed

    Bertozzi, Cara C; Schmaier, Alec A; Mericko, Patricia; Hess, Paul R; Zou, Zhiying; Chen, Mei; Chen, Chiu-Yu; Xu, Bin; Lu, Min-min; Zhou, Diane; Sebzda, Eric; Santore, Matthew T; Merianos, Demetri J; Stadtfeld, Matthias; Flake, Alan W; Graf, Thomas; Skoda, Radek; Maltzman, Jonathan S; Koretzky, Gary A; Kahn, Mark L

    2010-07-29

    Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.

  17. Regulation of brain insulin signaling: A new function for tau

    PubMed Central

    Gratuze, Maud; Planel, Emmanuel

    2017-01-01

    In this issue of JEM, Marciniak et al. (https://doi.org/10.1084/jem.20161731) identify a putative novel function of tau protein as a regulator of insulin signaling in the brain. They find that tau deletion impairs hippocampal response to insulin through IRS-1 and PTEN dysregulation and suggest that, in Alzheimer’s disease, impairment of brain insulin signaling might occur via tau loss of function. PMID:28652305

  18. Regulation of brain insulin signaling: A new function for tau.

    PubMed

    Gratuze, Maud; Planel, Emmanuel

    2017-08-07

    In this issue of JEM, Marciniak et al. (https://doi.org/10.1084/jem.20161731) identify a putative novel function of tau protein as a regulator of insulin signaling in the brain. They find that tau deletion impairs hippocampal response to insulin through IRS-1 and PTEN dysregulation and suggest that, in Alzheimer's disease, impairment of brain insulin signaling might occur via tau loss of function. © 2017 Gratuze and Planel.

  19. Signaling by Bone Morphogenetic Proteins directs formation of an ectodermal signaling center that regulates craniofacial development

    PubMed Central

    Foppiano, Silvia; Hu, Diane; Marcucio, Ralph S.

    2008-01-01

    We previously described a signaling center, the Frontonasal Ectodermal Zone (FEZ) that regulates growth and patterning of the frontonasal process (FNP). The FEZ is comprised of FNP ectoderm flanking a boundary between Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains. Our objective was to examine BMP signaling during formation of the FEZ. We blocked BMP signaling throughout the FNP prior to FEZ formation by infecting chick embryos at stage 10 (HH10) with a replication competent avian retrovirus encoding the BMP antagonist Noggin. We assessed gene expression patterns in the FNP 72 hours after infection (~HH22) and observed that Shh expression was reduced or absent. In the mesenchyme we observed that Bmp2 transcripts were absent while the Bmp4 expression domain was expanded proximally. In addition to the molecular changes, infected embryos also exhibited facial malformations at 72 and 96 hours after infection suggesting that the FEZ did not form. Our data indicate that reduced cell proliferation, but not apoptosis, in the mesenchyme contributed to the phenotype that we observed. Additionally, adding exogenous SHH into the mesenchyme of RCAS-Noggin infected embryos did not restore Bmp2 and Bmp4 to a normal pattern of expression. These data indicate that BMP signaling mediates interactions between tissues in the FNP that regulate FEZ formation; and that the correct pattern of Bmp2 and Bmp4, but not Bmp7, expression in the FNP mesenchyme requires signaling by the BMP pathway. PMID:18028903

  20. On the relation between photo- and gravitropically induced spatial memory in maize coleoptiles.

    PubMed

    Nick, P; Sailer, H; Schafer, E

    1990-06-01

    The interaction of photo- and gravitropic stimulation was studied by analysing the curvature of maize (Zea mays L.) coleoptiles subjected to rotation on horizontal clinostats. Gravitropic curvature in different directions with respect to the stimulation plane was found to be transient. This instability was caused by an increasing deviation of response direction from the stimulation plane towards the caryopsis. The bending angle as such, however, increased steadily. This reorientation of the gravitropic response towards the caryopsis is thought to be caused by the clinostat-elicited nastic curvature found in maize coleoptiles. In contrast, the response to phototropic stimulation was stable, in both, orientation and curving. Although stimulation by gravity was not capable of inducing a stable tropistic response, it could inhibit the response to opposing phototropic stimulation, if the counterstimulation was given more than 90 min after the onset of gravistimulation. For shorter time intervals the influence of the phototropic stimulus obscured the response to the first, gravitropic stimulation. For time intervals exceeding 90 min, however, the phototropic effects disappeared and the response was identical to that for gravity stimulation alone. This gravity-induced inhibition of the phototropic response was confined to the plane of gravity stimulation, because a phototropic stimulation in the perpendicular direction remained unaffected, irrespective of the time interval between the stimulations. This concerned not only the stable phototropic curving, but also the capacity of the phototropic induction to elicit a stable directional memory as described earlier (P. Nick and F. Schafer, 1988b, Planta 175, 380-388). This was tested by a second blue-light pulse opposing the first. It is suggested that gravity, too, can induce a directional memory differing from the blue-light elicited memory. The mechanisms mediating gravi- and phototropic directional memories are thought to

  1. NPH4, a Conditional Modulator of Auxin-Dependent Differential Growth Responses in Arabidopsis1

    PubMed Central

    Stowe-Evans, Emily L.; Harper, Reneé M.; Motchoulski, Andrei V.; Liscum, Emmanuel

    1998-01-01

    Although sessile in nature, plants are able to use a number of mechanisms to modify their morphology in response to changing environmental conditions. Differential growth is one such mechanism. Despite its importance in plant development, little is known about the molecular events regulating the establishment of differential growth. Here we report analyses of the nph4 (nonphototropic hypocotyl) mutants of Arabidopsis that suggest that the NPH4 protein plays a central role in the modulation of auxin-dependent differential growth. Results from physiological studies demonstrate that NPH4 activity is conditionally required for a number of differential growth responses, including phototropism, gravitropism, phytochrome-dependent hypocotyl curvature, apical hook maintenance, and abaxial/adaxial leaf-blade expansion. The nph4 mutants exhibited auxin resistance and severely impaired auxin-dependent gene expression, indicating that the defects associated with differential growth likely arise because of altered auxin responsiveness. Moreover, the auxin signaling events mediating phototropism are genetically correlated with the abundance of the NPH4 protein. PMID:9847100

  2. Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In

    2013-07-19

    Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediatedmore » IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways.« less

  3. A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice.

    PubMed

    Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

    2015-06-01

    Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. © 2015 American Society of Plant Biologists. All rights reserved.

  4. Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

    PubMed Central

    Ghosh, Arpan C.; O’Connor, Michael B.

    2014-01-01

    The ability to maintain cellular and physiological metabolic homeostasis is key for the survival of multicellular organisms in changing environmental conditions. However, our understanding of extracellular signaling pathways that modulate metabolic processes remains limited. In this study we show that the Activin-like ligand Dawdle (Daw) is a major regulator of systemic metabolic homeostasis and cellular metabolism in Drosophila. We find that loss of canonical Smad signaling downstream of Daw leads to defects in sugar and systemic pH homeostasis. Although Daw regulates sugar homeostasis by positively influencing insulin release, we find that the effect of Daw on pH balance is independent of its role in insulin signaling and is caused by accumulation of organic acids that are primarily tricarboxylic acid (TCA) cycle intermediates. RNA sequencing reveals that a number of TCA cycle enzymes and nuclear-encoded mitochondrial genes including genes involved in oxidative phosphorylation and β-oxidation are up-regulated in the daw mutants, indicating either a direct or indirect role of Daw in regulating these genes. These findings establish Activin signaling as a major metabolic regulator and uncover a functional link between TGF-β signaling, insulin signaling, and metabolism in Drosophila. PMID:24706779

  5. N-terminal nesprin-2 variants regulate β-catenin signalling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa

    2016-07-15

    The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragmentmore » of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.« less

  6. The nuclear lamina regulates germline stem cell niche organization via modulation of EGFR signaling.

    PubMed

    Chen, Haiyang; Chen, Xin; Zheng, Yixian

    2013-07-03

    Stem cell niche interactions have been studied extensively with regard to cell polarity and extracellular signaling. Less is known about the way in which signals and polarity cues integrate with intracellular structures to ensure appropriate niche organization and function. Here, we report that nuclear lamins function in the cyst stem cells (CySCs) of Drosophila testes to control the interaction of CySCs with the hub. This interaction is important for regulation of CySC differentiation and organization of the niche that supports the germline stem cells (GSCs). Lamin promotes nuclear retention of phosphorylated ERK in the CySC lineage by regulating the distribution of specific nucleoporins within the nuclear pores. Lamin-regulated nuclear epidermal growth factor (EGF) receptor signaling in the CySC lineage is essential for proliferation and differentiation of the GSCs and the transient amplifying germ cells. Thus, we have uncovered a role for the nuclear lamina in the integration of EGF signaling to regulate stem cell niche function. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Signaling through protein kinases and transcriptional regulators in Candida albicans.

    PubMed

    Dhillon, Navneet K; Sharma, Sadhna; Khuller, G K

    2003-01-01

    The human fungal pathogen Candida albicans switches from a budding yeast form to a polarized hyphal form in response to various external signals. This morphogenetic switching has been implicated in the development of pathogenicity. Several signaling pathways that regulate morphogenesis have been identified, including various transcription factors that either activate or repress hypha-specific genes. Two well-characterized pathways include the MAP kinase cascade and cAMP-dependent protein kinase pathway that regulate the transcription factors Cph1p and Efg1p, respectively. cAMP also appears to interplay with other second messengers: Ca2+, inositol tri-phosphates in regulating yeast-hyphal transition. Other, less-characterized pathways include two component histidine kinases, cyclin-dependent kinase pathway, and condition specific pathways such as pH and embedded growth conditions. Nrg1 and Rfg1 function as transcriptional repressors of hyphal genes via recruitment of Tup1 co-repressor complex. Different upstream signals converge into a common downstream output during hyphal switch. The levels of expression of several genes have been shown to be associated with hyphal morphogenesis rather than with a specific hypha-inducing condition. Hyphal development is also linked to the expression of a range of other virulence factors. This review explains the relative contribution of multiple pathways that could be used by Candida albican cells to sense subtle differences in the growth conditions of its native host environment.

  8. Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

    PubMed

    Belbin, Fiona E; Noordally, Zeenat B; Wetherill, Sarah J; Atkins, Kelly A; Franklin, Keara A; Dodd, Antony N

    2017-01-01

    We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  9. Synchronization of developmental processes and defense signaling by growth regulating transcription factors.

    PubMed

    Liu, Jinyi; Rice, J Hollis; Chen, Nana; Baum, Thomas J; Hewezi, Tarek

    2014-01-01

    Growth regulating factors (GRFs) are a conserved class of transcription factor in seed plants. GRFs are involved in various aspects of tissue differentiation and organ development. The implication of GRFs in biotic stress response has also been recently reported, suggesting a role of these transcription factors in coordinating the interaction between developmental processes and defense dynamics. However, the molecular mechanisms by which GRFs mediate the overlaps between defense signaling and developmental pathways are elusive. Here, we report large scale identification of putative target candidates of Arabidopsis GRF1 and GRF3 by comparing mRNA profiles of the grf1/grf2/grf3 triple mutant and those of the transgenic plants overexpressing miR396-resistant version of GRF1 or GRF3. We identified 1,098 and 600 genes as putative targets of GRF1 and GRF3, respectively. Functional classification of the potential target candidates revealed that GRF1 and GRF3 contribute to the regulation of various biological processes associated with defense response and disease resistance. GRF1 and GRF3 participate specifically in the regulation of defense-related transcription factors, cell-wall modifications, cytokinin biosynthesis and signaling, and secondary metabolites accumulation. GRF1 and GRF3 seem to fine-tune the crosstalk between miRNA signaling networks by regulating the expression of several miRNA target genes. In addition, our data suggest that GRF1 and GRF3 may function as negative regulators of gene expression through their association with other transcription factors. Collectively, our data provide new insights into how GRF1 and GRF3 might coordinate the interactions between defense signaling and plant growth and developmental pathways.

  10. C. elegans Notch signaling regulates adult chemosensory response and larval molting quiescence

    PubMed Central

    Singh, Komudi; Chao, Michael Y.; Somers, Gerard A.; Komatsu, Hidetoshi; Corkins, Mark E.; Larkins-Ford, Jonah; Tucey, Tim; Dionne, Heather M.; Walsh, Melissa B.; Beaumont, Emma K.; Hart, Douglas P.; Lockery, Shawn; Hart, Anne C.

    2011-01-01

    Summary Background The conserved DOS motif proteins OSM-7 and OSM-11 function as co-ligands with canonical DSL ligands to activate C. elegans Notch receptors during development. We report herein that Notch ligands, co-ligands and the receptors LIN-12 and GLP-1 regulate two C. elegans behaviors: chemosensory avoidance of octanol and quiescence during molting lethargus. Results C. elegans lacking osm-7 or osm-11 are defective in their response to octanol. We find that OSM-11 is secreted from hypodermal seam cells into the pseudocoelomic body cavity and acts non-cell autonomously as a diffusible factor. OSM-11 acts with the DSL ligand LAG-2 to activate LIN-12 and GLP-1 Notch receptors in the neurons of adult animals,- thereby regulating octanol avoidance response. In adult animals, over-expression of osm-11 and consequent Notch receptor activation induces anachronistic sleep-like quiescence. Perturbation of Notch signaling altered basal activity in adults as well as arousal thresholds and quiescence during molting lethargus. Genetic epistasis studies revealed that Notch signaling regulates quiescence via previously identified circuits and genetic pathways including the egl-4 cGMP-dependent kinase. Conclusions Our findings indicate that the conserved Notch pathway modulates behavior in adult C. elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans suggesting Notch may regulate sleep in other species. PMID:21549604

  11. Oxytocin in the regulation of social behaviours in medial amygdala-lesioned mice via the inhibition of the extracellular signal-regulated kinase signalling pathway.

    PubMed

    Wang, Yu; Zhao, Shanshan; Wu, Zhe; Feng, Yu; Zhao, Chuansheng; Zhang, Chaodong

    2015-05-01

    The neuropeptide oxytocin (OXT) has been implicated in the pathophysiology of behavioural deficits among patients with autism spectrum disorder (ASD). However, the molecular mechanisms underlying its role in ASD remain unclear. In the present study, a murine model with ASD-like phenotypes was induced by intra-medial amygdala injection of N-methyl-d-aspartate, and it was used to investigate the role of OXT in behaviour regulation. Behavioural tests were performed to verify the ASD-like phenotypes of N-methyl-d-aspartate-treated mice, and the results showed that mice with bilateral medial amygdala lesions presented significant behavioural deficits, including impaired learning and memory and increased anxiety and depression. We also observed a notably decreased level of OXT in both the plasma and the hypothalamus of medial amygdala-lesioned mice, and the extracellular signal-regulated kinase (ERK) was activated. Further studies demonstrated that the administration of OXT alleviated ASD-like symptoms and significantly inhibited phosphorylation of ERK; the inhibitory effect was similar to that of U0126, an ERK signalling inhibitor. In addition, OXT administration modulated the expression of downstream proteins of the ERK signalling pathway, such as cyclic adenosine monophosphate response element binding and c-fos. Taken together, our data indicate that OXT plays an important role in ameliorating behavioural deficits in an ASD-like mouse model, which was mediated by inhibiting the ERK signalling pathway and its downstream proteins. © 2015 Wiley Publishing Asia Pty Ltd.

  12. Redox Regulation of EGFR Signaling Through Cysteine Oxidation1

    PubMed Central

    Truong, Thu H.; Carroll, Kate S.

    2012-01-01

    Epidermal growth factor receptor (EGFR) exemplifies the family of receptor tyrosine kinases that mediate numerous cellular processes including growth, proliferation and differentiation. Moreover, gene amplification and EGFR mutations have been identified in a number of human malignancies, making this receptor an important target for the development of anticancer drugs. In addition to ligand-dependent activation and concomitant tyrosine phosphorylation, EGFR stimulation results in the localized generation of H2O2 by NADPH-dependent oxidases. In turn, H2O2 functions as a secondary messenger to regulate intracellular signaling cascades, largely through the modification of specific cysteine residues within redox-sensitive protein targets, including Cys797 in the EGFR active site. In this review, we highlight recent advances in our understanding of the mechanisms that underlie redox regulation of EGFR signaling and how these discoveries may form the basis for development of new therapeutic strategies to target this and other H2O2-modulated pathways. PMID:23186290

  13. Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

    PubMed Central

    Billaud, Marie; Lohman, Alexander W.; Johnstone, Scott R.; Biwer, Lauren A.; Mutchler, Stephanie; Isakson, Brant E.

    2014-01-01

    It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function. PMID:24671377

  14. Regulation of cellular communication by signaling microdomains in the blood vessel wall.

    PubMed

    Billaud, Marie; Lohman, Alexander W; Johnstone, Scott R; Biwer, Lauren A; Mutchler, Stephanie; Isakson, Brant E

    2014-01-01

    It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

  15. Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal.

    PubMed

    Angelotti, Tim; Daunt, David; Shcherbakova, Olga G; Kobilka, Brian; Hurt, Carl M

    2010-04-01

    Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

  16. CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways

    PubMed Central

    Wang, Chaoqun; Fok, Kin Lam; Cai, Zhiming; Chen, Hao; Chan, Hsiao Chang

    2017-01-01

    CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway. PMID:27902973

  17. CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways.

    PubMed

    Wang, Chaoqun; Fok, Kin Lam; Cai, Zhiming; Chen, Hao; Chan, Hsiao Chang

    2017-01-10

    CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway.

  18. Endocannabinoid Signaling, Glucocorticoid-Mediated Negative Feedback and Regulation of the HPA Axis

    PubMed Central

    Hill, M. N.; Tasker, J. G.

    2012-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis regulates the outflow of glucocorticoid hormones under basal conditions and in response to stress. Within the last decade, a large body of evidence has mounted indicating that the endocannabinoid system is involved in the central regulation of the stress response; however, the specific role endocannabinoid signalling plays in phases of HPA axis regulation, or the neural sites of action mediating this regulation, was not mapped out until recently. This review aims to collapse the current state of knowledge regarding the role of the endocannabinoid system in the regulation of the HPA axis to put together a working model of how and where endocannabinoids act within the brain to regulate outflow of the HPA axis. Specifically, we discuss the role of the endocannabinoid system in the regulation of the HPA axis under basal conditions, activation in response to acute stress and glucocorticoid-mediated negative feedback. Interestingly, there appears to be some anatomical specificity to the role of the endocannabinoid system in each phase of HPA axis regulation, as well as distinct roles of both anandamide and 2-arachidonoylglycerol in these phases. Ultimately, the current level of information indicates that endocannabinoid signalling acts to suppress HPA axis activity through concerted actions within the prefrontal cortex, amygdala and hypothalamus. PMID:22214537

  19. Brassinosteroid regulated kinases (BRKs) that mediate brassinosteroid signal transduction and uses thereof

    DOEpatents

    Wang, Zhi-Yong; Tang, Wenqiang

    2013-09-24

    The present invention identifies a novel family of kinases regulated by brassinosteroids, referred to as BRKs (brassinosteroid regulated kinases) or BSKs (brassinosteroid signaling kinases). The present invention provides methods for modulating the response of a plant cell to a brassinosteroid using BRKs.

  20. ROP GTPase-mediated auxin signaling regulates pavement cell interdigitation in Arabidopsis thaliana.

    PubMed

    Lin, Deshu; Ren, Huibo; Fu, Ying

    2015-01-01

    In multicellular plant organs, cell shape formation depends on molecular switches to transduce developmental or environmental signals and to coordinate cell-to-cell communication. Plants have a specific subfamily of the Rho GTPase family, usually called Rho of Plants (ROP), which serve as a critical signal transducer involved in many cellular processes. In the last decade, important advances in the ROP-mediated regulation of plant cell morphogenesis have been made by using Arabidopsis thaliana leaf and cotyledon pavement cells. Especially, the auxin-ROP signaling networks have been demonstrated to control interdigitated growth of pavement cells to form jigsaw-puzzle shapes. Here, we review findings related to the discovery of this novel auxin-signaling mechanism at the cell surface. This signaling pathway is to a large extent independent of the well-known Transport Inhibitor Response (TIR)-Auxin Signaling F-Box (AFB) pathway, and instead requires Auxin Binding Protein 1 (ABP1) interaction with the plasma membrane-localized, transmembrane kinase (TMK) receptor-like kinase to regulate ROP proteins. Once activated, ROP influences cytoskeletal organization and inhibits endocytosis of the auxin transporter PIN1. The present review focuses on ROP signaling and its self-organizing feature allowing ROP proteins to serve as a bustling signal decoder and integrator for plant cell morphogenesis. © 2014 Institute of Botany, Chinese Academy of Sciences.

  1. T Cell Calcium Signaling Regulation by the Co-Receptor CD5

    PubMed Central

    Freitas, Claudia M. Tellez

    2018-01-01

    Calcium influx is critical for T cell effector function and fate. T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca2+) concentration. Co-receptors stabilize interactions between the TCR and its ligand, the peptide-major histocompatibility complex (pMHC), and enhance Ca2+ signaling and T cell activation. Conversely, some co-receptors can dampen Ca2+ signaling and inhibit T cell activation. Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca2+ signaling and promote T cell survival. Similar to CTLA-4 and PD-1, the co-receptor CD5 has been known to act as a negative regulator of T cell activation and to alter Ca2+ signaling and T cell function. Though much is known about the role of CD5 in B cells, recent research has expanded our understanding of CD5 function in T cells. Here we review these recent findings and discuss how our improved understanding of CD5 Ca2+ signaling regulation could be useful for basic and clinical research. PMID:29701673

  2. Analysis of a developmentally regulated nuclear localization signal in Xenopus

    PubMed Central

    1992-01-01

    The 289 residue nuclear oncoprotein encoded by the adenovirus 5 Ela gene contains two peptide sequences that behave as nuclear localization signals (NLS). One signal, located at the carboxy terminus, is like many other known NLSs in that it consists of a short stretch of basic residues (KRPRP) and is constitutively active in cells. The second signal resides within an internal 45 residue region of E1a that contains few basic residues or sequences that resemble other known NLSs. Moreover, this internal signal functions in injected Xenopus oocytes, but not in transfected Xenopus A6 cells, suggesting that it could be regulated developmentally (Slavicek et al. 1989. J. Virol. 63:4047). In this study, we show that the activity of this signal is sensitive to ATP depletion in vivo, efficiently directs the import of a 50 kD fusion protein and can compete with the E1a carboxy-terminal NLS for nuclear import. In addition, we have delineated the precise amino acid residues that comprise the second E1a NLS, and have assessed its utilization during Xenopus embryogenesis. Using amino acid deletion and substitution analyses, we show that the signal consists of the sequence FV(X)7-20MXSLXYM(X)4MF. By expressing in Xenopus embryos a truncated E1a protein that contains only the second NLS and by monitoring its cytoplasmic/nuclear distribution during development with indirect immunofluorescence, we find that the second NLS is utilized up to the early neurula stage. In addition, there appears to be a hierarchy among the embryonic germ layers as to when the second NLS becomes nonfunctional. For this reason, we refer to this NLS as the developmentally regulated nuclear localization signal (drNLS). The implications of these findings for early development are discussed. PMID:1387407

  3. Ro52-mediated Monoubiquitination of IKKβ Down-regulates NF-κB Signalling

    PubMed Central

    Wada, Keiji; Niida, Motoko; Tanaka, Makoto; Kamitani, Tetsu

    2009-01-01

    Upon activation, NF-κB translocates into the nucleus and initiates biological events. This NF-κB signalling is mainly regulated by the protein kinase IKKβ. Early in this signalling pathway, IKKβ is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of HTLV-1. In cells infected by HTLV-1, IKKβ is persistently phosphorylated and conjugated with monoubiquitin due to Tax expression. Although this Tax-induced monoubiquitination appears to be an important regulation system for IKKβ, how the monoubiquitination occurs is unknown and its role in NF-κB signalling is still unclear. Here, we show that an E3-ubiquitin ligase Ro52 interacts weakly with wild-type IKKβ but strongly with a phosphomimetic mutant IKKβ to conjugate monoubiquitin in cooperation with an E2-ubiquitin-conjugating enzyme UbcH5B. These results suggest that the Tax-induced phosphorylation of IKKβ causes an interaction with Ro52 for the subsequent monoubiquitination. NF-κB reporter assays have shown that the IKKβ activity is suppressed by wild-type Ro52, but not by its inactive mutant. In addition, monoubiquitin fusion of IKKβ reduced its activity for NF-κB signalling. We also found that Ro52 dramatically reduces the level of Tax. These results suggest that Ro52 down-regulates Tax-induced NF-κB signalling by monoubiquitinating IKKβ and by reducing the level of Tax. PMID:19675099

  4. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

    DOE PAGES

    Dole, Neha S.; Mazur, Courtney M.; Acevedo, Claire; ...

    2017-11-28

    Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/-), wemore » show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Resistance to fracture requires healthy bone mass and quality. However, the cellular mechanisms regulating bone quality are unclear. Dole et al. show that osteocyte-intrinsic TGF-β signaling maintains bone quality through perilacunar/canalicular remodeling. Thus, osteocytes mediate perilacunar/canalicular remodeling and osteoclast-directed remodeling to cooperatively maintain bone quality and mass and prevent fragility.« less

  5. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dole, Neha S.; Mazur, Courtney M.; Acevedo, Claire

    Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/-), wemore » show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Resistance to fracture requires healthy bone mass and quality. However, the cellular mechanisms regulating bone quality are unclear. Dole et al. show that osteocyte-intrinsic TGF-β signaling maintains bone quality through perilacunar/canalicular remodeling. Thus, osteocytes mediate perilacunar/canalicular remodeling and osteoclast-directed remodeling to cooperatively maintain bone quality and mass and prevent fragility.« less

  6. Lipid anchoring of Arabidopsis phototropin 1 to assess the functional significance of receptor internalization: should I stay or should I go?

    PubMed

    Preuten, Tobias; Blackwood, Lisa; Christie, John M; Fankhauser, Christian

    2015-05-01

    The phototropin 1 (phot1) blue light receptor mediates a number of adaptive responses, including phototropism, that generally serve to optimize photosynthetic capacity. Phot1 is a plasma membrane-associated protein, but upon irradiation, a fraction is internalized into the cytoplasm. Although this phenomenon has been reported for more than a decade, its biological significance remains elusive. Here, we use a genetic approach to revisit the prevalent hypotheses regarding the functional importance of receptor internalization. Transgenic plants expressing lipidated versions of phot1 that are permanently anchored to the plasma membrane were used to analyse the effect of internalization on receptor turnover, phototropism and other phot1-mediated responses. Myristoylation and farnesylation effectively prevented phot1 internalization. Both modified photoreceptors were found to be fully functional in Arabidopsis, rescuing phototropism and all other phot1-mediated responses tested. Light-mediated phot1 turnover occurred as in the native receptor. Furthermore, our work does not provide any evidence of a role of phot1 internalization in the attenuation of receptor signalling during phototropism. Our results demonstrate that phot1 signalling is initiated at the plasma membrane. They furthermore indicate that release of phot1 into the cytosol is not linked to receptor turnover or desensitization. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  7. Roles and regulations of Hippo signaling during preimplantation mouse development.

    PubMed

    Sasaki, Hiroshi

    2017-01-01

    During preimplantation development, mouse embryos form two types of cells, the trophoectoderm (TE) and inner cell mass (ICM), by the early blastocyst stage. This process does not require maternal factors localized in the zygotes, and embryos self-organize at the blastocyst stage through intercellular communications. In terms of the mechanisms of cell fate specification, three historical models have been proposed: the positional model, and the original and newer versions of the polarity model. Recent studies have revealed that the intercellular Hippo signaling pathway plays a central role in the specification of the first cell fates. Hippo signaling is active in the inner cells but inactive in the outer cells. The Hippo-active inner and Hippo-inactive outer cells take the fates of the ICM and the TE, respectively. At the 32-cell stage, E-cadherin-mediated cell-cell adhesion and cell polarization by the Par-aPKC system activates and inactivates the Hippo pathway, respectively. Both mechanisms involve regulation of angiomotin, and cooperation of these mechanisms establishes cell position-dependent activation of Hippo signaling. At the 16-cell stage, however, asymmetric cell division produces the initial differences in Hippo signaling. At this stage, cell polarity is controlled by both Par-aPKC-dependent and -independent mechanisms. All three historical models are explained by the different regulations and roles of Hippo signaling. Based on these findings, I would like to propose the model by which the differences in Hippo signaling among blastomeres is first produced by asymmetric cell division and then enhanced and stabilized by cell position-dependent mechanisms until their fates are fixed. © 2016 Japanese Society of Developmental Biologists.

  8. Karrikins: Regulators Involved in Phytohormone Signaling Networks during Seed Germination and Seedling Development

    PubMed Central

    Meng, Yongjie; Shuai, Haiwei; Luo, Xiaofeng; Chen, Feng; Zhou, Wenguan; Yang, Wenyu; Shu, Kai

    2017-01-01

    Seed germination and early seedling establishment are critical stages during a plant’s life cycle. These stages are precisely regulated by multiple internal factors, including phytohormones and environmental cues such as light. As a family of small molecules discovered in wildfire smoke, karrikins (KARs) play a key role in various biological processes, including seed dormancy release, germination regulation, and seedling establishment. KARs show a high similarity with strigolactone (SL) in both chemical structure and signaling transduction pathways. Current evidence shows that KARs may regulate seed germination by mediating the biosynthesis and/or signaling transduction of abscisic acid (ABA), gibberellin (GA) and auxin [indoleacetic acid (IAA)]. Interestingly, KARs regulate seed germination differently in different species. Furthermore, the promotion effect on seedling establishment implies that KARs have a great potential application in alleviating shade avoidance response, which attracts more and more attention in plant molecular biology. In these processes, KARs may have complicated interactions with phytohormones, especially with IAA. In this updated review, we summarize the current understanding of the relationship between KARs and SL in the chemical structure, signaling pathway and the regulation of plant growth and development. Further, the crosstalk between KARs and phytohormones in regulating seed germination and seedling development and that between KARs and IAA during shade responses are discussed. Finally, future challenges and research directions for the KAR research field are suggested. PMID:28174573

  9. Hedgehog Is a Positive Regulator of FGF Signalling during Embryonic Tracheal Cell Migration

    PubMed Central

    Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J.

    2014-01-01

    Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration. PMID:24651658

  10. Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration.

    PubMed

    Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J

    2014-01-01

    Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration.

  11. A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice[OPEN

    PubMed Central

    Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

    2015-01-01

    Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. PMID:26002868

  12. Signaling hierarchy regulating human endothelial cell development.

    PubMed

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  13. Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.

    PubMed

    Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed

    2017-08-04

    Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.

  14. Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons

    PubMed Central

    Cohen, Matthew R.; Johnson, William M.; Pilat, Jennifer M.; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E.

    2015-01-01

    Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca2+-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca2+-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca2+ signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca2+ signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. PMID:26416880

  15. Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system

    PubMed Central

    Kim, Teayoun; Yang, Qinglin

    2013-01-01

    Peroxisome-proliferator-activated receptors (PPARs) comprise three subtypes (PPARα, δ and γ) to form a nuclear receptor superfamily. PPARs act as key transcriptional regulators of lipid metabolism, mitochondrial biogenesis, and anti-oxidant defense. While their roles in regulating lipid metabolism have been well established, the role of PPARs in regulating redox activity remains incompletely understood. Since redox activity is an integral part of oxidative metabolism, it is not surprising that changes in PPAR signaling in a specific cell or tissue will lead to alteration of redox state. The effects of PPAR signaling are directly related to PPAR expression, protein activities and PPAR interactions with their coregulators. The three subtypes of PPARs regulate cellular lipid and energy metabolism in most tissues in the body with overlapping and preferential effects on different metabolic steps depending on a specific tissue. Adding to the complexity, specific ligands of each PPAR subtype may also display different potencies and specificities of their role on regulating the redox pathways. Moreover, the intensity and extension of redox regulation by each PPAR subtype are varied depending on different tissues and cell types. Both beneficial and adverse effects of PPAR ligands against cardiovascular disorders have been extensively studied by many groups. The purpose of the review is to summarize the effects of each PPAR on regulating redox and the underlying mechanisms, as well as to discuss the implications in the cardiovascular system. PMID:23802046

  16. Plant phospholipase C family: Regulation and functional role in lipid signaling.

    PubMed

    Singh, Amarjeet; Bhatnagar, Nikita; Pandey, Amita; Pandey, Girdhar K

    2015-08-01

    Phospholipase C (PLC), a major membrane phospholipid hydrolyzing enzyme generates signaling messengers such as diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) in animals, and their phosphorylated forms such as phosphatidic acid (PA) and inositol hexakisphosphate (IP6) are thought to regulate various cellular processes in plants. Based on substrate specificity, plant PLC family is sub-divided into phosphatidylinositol-PLC (PI-PLC) and phosphatidylcholine-PLC (PC-PLC) groups. The activity of plant PLCs is regulated by various factors and the major ones include, Ca(2+) concentration, phospholipid substrate, post-translational modifications and interacting proteins. Most of the PLC members have been localized at the plasma membrane, suited for their function of membrane lipid hydrolysis. Several PLC members have been implicated in various cellular processes and signaling networks, triggered in response to a number of environmental cues and developmental events in different plant species, which makes them potential candidates for genetically engineering the crop plants for stress tolerance and enhancing the crop productivity. In this review article, we are focusing mainly on the plant PLC signaling and regulation, potential cellular and physiological role in different abiotic and biotic stresses, nutrient deficiency, growth and development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Calcium dynamics and signaling in vascular regulation: computational models

    PubMed Central

    Tsoukias, Nikolaos Michael

    2013-01-01

    Calcium is a universal signaling molecule with a central role in a number of vascular functions including in the regulation of tone and blood flow. Experimentation has provided insights into signaling pathways that lead to or affected by Ca2+ mobilization in the vasculature. Mathematical modeling offers a systematic approach to the analysis of these mechanisms and can serve as a tool for data interpretation and for guiding new experimental studies. Comprehensive models of calcium dynamics are well advanced for some systems such as the heart. This review summarizes the progress that has been made in modeling Ca2+ dynamics and signaling in vascular cells. Model simulations show how Ca2+ signaling emerges as a result of complex, nonlinear interactions that cannot be properly analyzed using only a reductionist's approach. A strategy of integrative modeling in the vasculature is outlined that will allow linking macroscale pathophysiological responses to the underlying cellular mechanisms. PMID:21061306

  18. Wnt signaling regulates pulp volume and dentin thickness

    PubMed Central

    Lim, Won Hee; Liu, Bo; Cheng, Du; Hunter, Daniel J; Zhong, Zhendong; Ramos, Daniel M; Williams, Bart O; Sharpe, Paul T; Bardet, Claire; Mah, Su-jung; Helms, Jill A

    2015-01-01

    Odontoblasts, cementoblasts, ameloblasts and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wingless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin, which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN-Cre;Wlsfl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt-mediated mis-regulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits DSP; this inhibition must be relieved for odontoblasts to differentiate. In OCN-Cre;Wlsfl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2-mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex. PMID:23996396

  19. Messages from the voices within: regulation of signaling by proteins of the nuclear lamina.

    PubMed

    Gerace, Larry; Tapia, Olga

    2018-01-04

    The nuclear lamina (NL) is a protein scaffold lining the nuclear envelope that consists of nuclear lamins and associated transmembrane proteins. It helps to organize the nuclear envelope, chromosomes, and the cytoplasmic cytoskeleton. The NL also has an important role in regulation of signaling, as highlighted by the wide range of human diseases caused by mutations in the genes for NL proteins with associated signaling defects. This review will consider diverse mechanisms for signaling regulation by the NL that have been uncovered recently, including interaction with signaling effectors, modulation of actin assembly and compositional alteration of the NL. Cells with discrete NL mutations often show disruption of multiple signaling pathways, however, and for the most part the mechanistic basis for these complex phenotypes remains to be elucidated. Copyright © 2017. Published by Elsevier Ltd.

  20. [Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

    PubMed

    Xiao, Ya-Ping; Zeng, Jie; Jiao, Lin-Na; Xu, Xiao-Yu

    2018-01-01

    The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ β -catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ β -catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. Copyright© by the Chinese Pharmaceutical Association.

  1. Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche

    PubMed Central

    Wang, Su; Gao, Yuan; Song, Xiaoqing; Ma, Xing; Zhu, Xiujuan; Mao, Ying; Yang, Zhihao; Ni, Jianquan; Li, Hua; Malanowski, Kathryn E; Anoja, Perera; Park, Jungeun; Haug, Jeff; Xie, Ting

    2015-01-01

    Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche. DOI: http://dx.doi.org/10.7554/eLife.08174.001 PMID:26452202

  2. Porcine circovirus type 2 replication is impaired by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wei Li; Liu Jue

    Postweaning multisystemic wasting syndrome, which is primarily caused by porcine circovirus type 2 (PCV2), is an emerging and important swine disease. We have recently shown that PCV2 induces nuclear factor kappa B activation and its activation is required for active replication, but the other cellular factors involved in PCV2 replication are not well defined. The extracellular signal-regulated kinase (ERK) which served as an important component of cellular signal transduction pathways has been shown to regulate many viral infections. In this report, we show that PCV2 activates ERK1/2 in PCV2-infected PK15 cells dependent on viral replication. The PCV2-induced ERK1/2 leads tomore » phosphorylation of the ternary complex factor Elk-1, which kinetically paralleled ERK1/2 activation. Inhibition of ERK activation with U0126, a specific MEK1/2 inhibitor, significantly reduced viral progeny release. Investigations into the mechanism of ERK1/2 regulation revealed that inhibition of ERK activation leads to decreased viral transcription and lower virus protein expression. These data indicate that the ERK signaling pathway is involved in PCV2 infection and beneficial to PCV2 replication in the cultured cells.« less

  3. An investigation of the phototropic effect on seedling orientation in a microgravity environment: A student involvement project. [radish germination

    NASA Technical Reports Server (NTRS)

    Barainca, J. W.

    1984-01-01

    A microgravity growth chamber was designed to investigate the phototropic response of radish seedlings. Enclosed in a one fourth inch thick, hexagonal, fiberglass-foam spacepak nineteen inches across corners, the experiment consists of a growth chamber and germination tray, a water reservoir and solenoid valve, a fluorescent light for photo simulation, a Minolta X700 camera with programmable back, a 50 mm macro lens and flash, a battery pack, and a computer controller. Two temperature sensors and one light sensor located in the walls of the growth chamber provide temperature and illumination data. A computer provides 8 K command and 34 K data storage capability. The experiment was not activated during the STS flight because a malfunctioning latching relay stuck and reduced the battery power level.

  4. Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

    NASA Technical Reports Server (NTRS)

    Swarthout, John T.; D'Alonzo, Richard C.; Selvamurugan, Nagarajan; Partridge, Nicola C.

    2002-01-01

    Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific

  5. Phytotoxin production in Aspergillus terreus is regulated by independent environmental signals

    PubMed Central

    Gressler, Markus; Meyer, Florian; Heine, Daniel; Hortschansky, Peter; Hertweck, Christian; Brock, Matthias

    2015-01-01

    Secondary metabolites have a great potential as pharmaceuticals, but there are only a few examples where regulation of gene cluster expression has been correlated with ecological and physiological relevance for the producer. Here, signals, mediators, and biological effects of terrein production were studied in the fungus Aspergillus terreus to elucidate the contribution of terrein to ecological competition. Terrein causes fruit surface lesions and inhibits plant seed germination. Additionally, terrein is moderately antifungal and reduces ferric iron, thereby supporting growth of A. terreus under iron starvation. In accordance, the lack of nitrogen or iron or elevated methionine levels induced terrein production and was dependent on either the nitrogen response regulators AreA and AtfA or the iron response regulator HapX. Independent signal transduction allows complex sensing of the environment and, combined with its broad spectrum of biological activities, terrein provides a prominent example of adapted secondary metabolite production in response to environmental competition. DOI: http://dx.doi.org/10.7554/eLife.07861.001 PMID:26173180

  6. Coordinated Regulation of Insulin Signaling by the Protein Tyrosine Phosphatases PTP1B and TCPTP

    PubMed Central

    Galic, Sandra; Hauser, Christine; Kahn, Barbara B.; Haj, Fawaz G.; Neel, Benjamin G.; Tonks, Nicholas K.; Tiganis, Tony

    2005-01-01

    The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. Galic, M. Klingler-Hoffmann, M. T. Fodero-Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks, and T. Tiganis, Mol. Cell. Biol. 23:2096-2108, 2003). Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling. Whereas insulin-induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP−/− and PTP1B−/− immortalized mouse embryo fibroblasts (MEFs), mitogen-activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs. By using phosphorylation-specific antibodies, we demonstrate that both IR β-subunit Y1162/Y1163 and Y972 phosphorylation are elevated in PTP1B−/− MEFs, whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP−/− MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of IR phosphorylation and signaling. Consistent with this, suppression of TCPTP protein levels by RNA interference in PTP1B−/− MEFs resulted in no change in ERK1/2 signaling but caused prolonged Akt activation and Y1162/Y1163 phosphorylation. These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell. PMID:15632081

  7. Regulation of potassium transport and signaling in plants.

    PubMed

    Wang, Yi; Wu, Wei-Hua

    2017-10-01

    As an essential macronutrient, potassium (K + ) plays crucial roles in diverse physiological processes during plant growth and development. The K + concentration in soils is relatively low and fluctuating. Plants are able to perceive external K + changes and generate chemical and physical signals in plant cells. The signals can be transducted across the plasma membrane and into the cytosol, and eventually regulates the downstream targets, particularly K + channels and transporters. As a result, K + homeostasis in plant cells is modulated, which facilitates plant adaptation to K + deficient conditions. This minireview focuses on the latest research progress in the diverse functions of K + channels and transporters as well as their regulatory mechanisms in plant response to low-K + stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Fibroblast growth factor (Fgf) signaling pathway regulates liver homeostasis in zebrafish.

    PubMed

    Tsai, Su-Mei; Liu, Da-Wei; Wang, Wen-Pin

    2013-04-01

    In mammals, fibroblast growth factor (FGF) signaling controls liver specification and regulates the metabolism of lipids, cholesterol, and bile acids. FGF signaling also promotes hepatocyte proliferation, and helps detoxify hepatotoxin during liver regeneration after partial hepatectomy. However, the function of Fgf in zebrafish liver is not yet well understood, specifically for postnatal homeostasis. The current study analyzed the expression of fgf receptors (fgfrs) in the liver of zebrafish. We then investigated the function of Fgf signaling in the zebrafish liver by expressing a dominant-negative Fgf receptor in hepatocytes (lfabp:dnfgfr1-egfp, lf:dnfr). Histological analysis showed that our genetic intervention resulted in a small liver size with defected medial expansion of developing livers in transgenic (Tg) larvae. Morphologically, the liver lobe of lf:dnfr adult fish was shorter than that of control. Ballooning degeneration of hepatocytes was observed in fish as young as 3 months. Further examination revealed the development of hepatic steatosis and cholestasis. In adult Tg fish, we unexpectedly observed increased liver-to-body-weight ratios, with higher percentages of proliferating hepatocytes. Considering all these findings, we concluded that as in mammals, in adult zebrafish the metabolism of lipid and bile acids in the liver are regulated by Fgf signaling. Disruption of the Fgf signal-mediated metabolism might indirectly affect hepatocyte proliferation.

  9. The Golgi in Cell Migration: Regulation by Signal Transduction and Its Implications for Cancer Cell Metastasis

    PubMed Central

    Millarte, Valentina; Farhan, Hesso

    2012-01-01

    Migration and invasion are fundamental features of metastatic cancer cells. The Golgi apparatus, an organelle involved in posttranslational modification and sorting of proteins, is widely accepted to regulate directional cell migration. In addition, mounting evidence suggests that the Golgi is a hub for different signaling pathways. In this paper we will give an overview on how polarized secretion and microtubule nucleation at the Golgi regulate directional cell migration. We will review different signaling pathways that signal to and from the Golgi. Finally, we will discuss how these signaling pathways regulate the role of the Golgi in cell migration and invasion. We propose that by identifying regulators of the Golgi, we might be able to uncover unappreciated modulators of cell migration. Uncovering the regulatory network that orchestrates cell migration is of fundamental importance for the development of new therapeutic strategies against cancer cell metastasis. PMID:22623902

  10. Regulation of early Xenopus development by ErbB signaling

    PubMed Central

    Nie, Shuyi; Chang, Chenbei

    2008-01-01

    ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2 and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements and embryonic patterning during early Xenopus development. PMID:16258939

  11. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira.

    PubMed

    Adhikarla, Haritha; Wunder, Elsio A; Mechaly, Ariel E; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I

    2018-01-01

    Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira . In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator ) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one ( lvrB ) or both genes ( lvrA/B ) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium.

  12. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

    PubMed Central

    Adhikarla, Haritha; Wunder, Elsio A.; Mechaly, Ariel E.; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P.; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I.

    2018-01-01

    Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium. PMID:29600195

  13. Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

    PubMed

    Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

    2017-06-01

    Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Dynamic ubiquitin signaling in cell cycle regulation

    PubMed Central

    Gilberto, Samuel

    2017-01-01

    The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. PMID:28684425

  15. Dynamic ubiquitin signaling in cell cycle regulation.

    PubMed

    Gilberto, Samuel; Peter, Matthias

    2017-08-07

    The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. © 2017 Gilberto and Peter.

  16. HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA.

    PubMed

    He, Tian-Sheng; Chen, Tian; Wang, Dan-Dan; Xu, Liang-Guo

    2018-06-15

    Mitochondrial anti‑viral signaling protein (VISA), additionally termed MAVS, IPS‑1 and Cardif, is located at the outer membrane of mitochondria and is an essential adaptor in the Rig‑like receptor (RLRs) signaling pathway. Upon viral infection, activated RLRs interact with VISA on mitochondria, forming a RLR‑VISA platform, leading to the recruitment of different TRAF family members, including TRAF3, TRAF2 and TRAF6. This results in the phosphorylation and nuclear translocation of interferon regulatory factors 3 and 7 (IRF3/IRF7) by TANK binding kinase 1 (TBK1) and/or IKKε, as well as activation of NF‑κB, to induce type I interferons (IFNs) and pro‑inflammatory cytokines. It remains to be elucidated how VISA functions as a scaffold for protein complex assembly in mitochondria to regulate RLR‑VISA antiviral signaling. In the present study, it was demonstrated that HAUS augmin like complex subunit 8 (HAUS8) augments the RLR‑VISA‑dependent antiviral signaling pathway by targeting the VISA complex. Co‑immunoprecipitation verified that HAUS8 was associated with VISA and the VISA signaling complex components retinoic acid‑inducible gene I (RIG‑I) and TBK1 when the RLR‑VISA signaling pathway was activated. The data demonstrated that overexpression of HAUS8 significantly promoted the activity of the transcription factors NF‑κB, IRF3 and the IFN‑β promoter induced by Sendai virus‑mediated RLR‑VISA signaling. HAUS8 increased the polyubiquitination of VISA, RIG‑I and TBK1. Knockdown of HAUS8 inhibited the activation of the transcription factors IRF‑3, NF‑κB and the IFN‑β promoter triggered by Sendai virus. Collectively, these results demonstrated that HAUS8 may function as a positive regulator of RLR‑VISA dependent antiviral signaling by targeting the VISA complex, providing a novel regulatory mechanism of antiviral responses.

  17. RNA sensor LGP2 inhibits TRAF ubiquitin ligase to negatively regulate innate immune signaling.

    PubMed

    Parisien, Jean-Patrick; Lenoir, Jessica J; Mandhana, Roli; Rodriguez, Kenny R; Qian, Kenin; Bruns, Annie M; Horvath, Curt M

    2018-06-01

    The production of type I interferon (IFN) is essential for cellular barrier functions and innate and adaptive antiviral immunity. In response to virus infections, RNA receptors RIG-I and MDA5 stimulate a mitochondria-localized signaling apparatus that uses TRAF family ubiquitin ligase proteins to activate master transcription regulators IRF3 and NFκB, driving IFN and antiviral target gene expression. Data indicate that a third RNA receptor, LGP2, acts as a negative regulator of antiviral signaling by interfering with TRAF family proteins. Disruption of LGP2 expression in cells results in earlier and overactive transcriptional responses to virus or dsRNA LGP2 associates with the C-terminus of TRAF2, TRAF3, TRAF5, and TRAF6 and interferes with TRAF ubiquitin ligase activity. TRAF interference is independent of LGP2 ATP hydrolysis, RNA binding, or its C-terminal domain, and LGP2 can regulate TRAF-mediated signaling pathways in trans , including IL-1β, TNFα, and cGAMP These findings provide a unique mechanism for LGP2 negative regulation through TRAF suppression and extend the potential impact of LGP2 negative regulation beyond the IFN antiviral response. © 2018 The Authors.

  18. Plant elicitor peptides are conserved signals regulating direct and indirect antiherbivore defense

    PubMed Central

    Huffaker, Alisa; Pearce, Gregory; Veyrat, Nathalie; Erb, Matthias; Turlings, Ted C. J.; Sartor, Ryan; Shen, Zhouxin; Briggs, Steven P.; Vaughan, Martha M.; Alborn, Hans T.; Teal, Peter E. A.; Schmelz, Eric A.

    2013-01-01

    Insect-induced defenses occur in nearly all plants and are regulated by conserved signaling pathways. As the first described plant peptide signal, systemin regulates antiherbivore defenses in the Solanaceae, but in other plant families, peptides with analogous activity have remained elusive. In the current study, we demonstrate that a member of the maize (Zea mays) plant elicitor peptide (Pep) family, ZmPep3, regulates responses against herbivores. Consistent with being a signal, expression of the ZmPROPEP3 precursor gene is rapidly induced by Spodoptera exigua oral secretions. At concentrations starting at 5 pmol per leaf, ZmPep3 stimulates production of jasmonic acid, ethylene, and increased expression of genes encoding proteins associated with herbivory defense. These include proteinase inhibitors and biosynthetic enzymes for production of volatile terpenes and benzoxazinoids. In accordance with gene expression data, plants treated with ZmPep3 emit volatiles similar to those from plants subjected to herbivory. ZmPep3-treated plants also exhibit induced accumulation of the benzoxazinoid phytoalexin 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside. Direct and indirect defenses induced by ZmPep3 contribute to resistance against S. exigua through significant reduction of larval growth and attraction of Cotesia marginiventris parasitoids. ZmPep3 activity is specific to Poaceous species; however, peptides derived from PROPEP orthologs identified in Solanaceous and Fabaceous plants also induce herbivory-associated volatiles in their respective species. These studies demonstrate that Peps are conserved signals across diverse plant families regulating antiherbivore defenses and are likely to be the missing functional homologs of systemin outside of the Solanaceae. PMID:23509266

  19. CASK regulates CaMKII autophosphorylation in neuronal growth, calcium signaling, and learning

    PubMed Central

    Gillespie, John M.; Hodge, James J. L.

    2013-01-01

    Calcium (Ca2+)/calmodulin (CaM)-dependent kinase II (CaMKII) activity plays a fundamental role in learning and memory. A key feature of CaMKII in memory formation is its ability to be regulated by autophosphorylation, which switches its activity on and off during synaptic plasticity. The synaptic scaffolding protein CASK (calcium (Ca2+)/calmodulin (CaM) associated serine kinase) is also important for learning and memory, as mutations in CASK result in intellectual disability and neurological defects in humans. We show that in Drosophila larvae, CASK interacts with CaMKII to control neuronal growth and calcium signaling. Furthermore, deletion of the CaMK-like and L27 domains of CASK (CASK β null) or expression of overactive CaMKII (T287D) produced similar effects on synaptic growth and Ca2+ signaling. CASK overexpression rescues the effects of CaMKII overactivity, consistent with the notion that CASK and CaMKII act in a common pathway that controls these neuronal processes. The reduction in Ca2+ signaling observed in the CASK β null mutant caused a decrease in vesicle trafficking at synapses. In addition, the decrease in Ca2+ signaling in CASK mutants was associated with an increase in Ether-à-go-go (EAG) potassium (K+) channel localization to synapses. Reducing EAG restored the decrease in Ca2+ signaling observed in CASK mutants to the level of wildtype, suggesting that CASK regulates Ca2+ signaling via EAG. CASK knockdown reduced both appetitive associative learning and odor evoked Ca2+ responses in Drosophila mushroom bodies, which are the learning centers of Drosophila. Expression of human CASK in Drosophila rescued the effect of CASK deletion on the activity state of CaMKII, suggesting that human CASK may also regulate CaMKII autophosphorylation. PMID:24062638

  20. Rice PLASTOCHRON genes regulate leaf maturation downstream of the gibberellin signal transduction pathway.

    PubMed

    Mimura, Manaki; Nagato, Yasuo; Itoh, Jun-Ichi

    2012-05-01

    Rice PLASTOCHRON 1 (PLA1) and PLA2 genes regulate leaf maturation and plastochron, and their loss-of-function mutants exhibit small organs and rapid leaf emergence. They encode a cytochrome P450 protein CYP78A11 and an RNA-binding protein, respectively. Their homologs in Arabidopsis and maize are also associated with plant development/organ size. Despite the importance of PLA genes in plant development, their molecular functions remain unknown. Here, we investigated how PLA1 and PLA2 genes are related to phytohormones. We found that gibberellin (GA) is the major phytohormone that promotes PLA1 and PLA2 expression. GA induced PLA1 and PLA2 expression, and conversely the GA-inhibitor uniconazole suppressed PLA1 and PLA2 expression. In pla1-4 and pla2-1 seedlings, expression levels of GA biosynthesis genes and the signal transduction gene were similar to those in wild-type seedlings. GA treatment slightly down-regulated the GA biosynthesis gene GA20ox2 and up-regulated the GA-catabolizing gene GA2ox4, whereas the GA biosynthesis inhibitor uniconazole up-regulated GA20ox2 and down-regulated GA2ox4 both in wild-type and pla mutants, suggesting that the GA feedback mechanism is not impaired in pla1 and pla2. To reveal how GA signal transduction affects the expression of PLA1 and PLA2, PLA expression in GA-signaling mutants was examined. In GA-insensitive mutant, gid1 and less-sensitive mutant, Slr1-d1, PLA1 and PLA2 expression was down-regulated. On the other hand, the expression levels of PLA1 and PLA2 were highly enhanced in a GA-constitutive-active mutant, slr1-1, causing ectopic overexpression. These results indicate that both PLA1 and PLA2 act downstream of the GA signal transduction pathway to regulate leaf development.

  1. Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

    PubMed

    Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

    2015-02-01

    Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Identification of DreI as an Antiviral Factor Regulated by RLR Signaling Pathway

    PubMed Central

    Li, Shun; Sun, Fan; Zhang, Yi-Bing; Gui, Jian-Fang; Zhang, Qi-Ya

    2012-01-01

    Background Retinoic acid-inducible gene I (RIG-I)–like receptors (RLRs) had been demonstrated to prime interferon (IFN) response against viral infection via the conserved RLR signaling in fish, and a novel fish-specific gene, the grass carp reovirus (GCRV)-induced gene 2 (Gig2), had been suggested to play important role in host antiviral response. Methodology/Principal Findings In this study, we cloned and characterized zebrafish Gig2 homolog (named Danio rerio Gig2-I, DreI), and revealed its antiviral role and expressional regulation signaling pathway. RT-PCR, Western blot and promoter activity assay indicate that DreI can be induced by poly I:C, spring viremia of carp virus (SVCV) and recombinant IFN (rIFN), showing that DreI is a typical ISG. Using the pivotal signaling molecules of RLR pathway, including RIG-I, MDA5 and IRF3 from crucian carp, it is found that DreI expression is regulated by RLR cascade and IRF3 plays an important role in this regulation. Furthermore, promoter mutation assay confirms that the IFN-stimulated regulatory elements (ISRE) in the 5′ flanking region of DreI is essential for its induction. Finally, overexpression of DreI leads to establish a strong antiviral state against SVCV and Rana grylio virus (RGV) infection in EPC (Epithelioma papulosum cyprinid) cells. Conclusions/Significance These data indicate that DreI is an antiviral protein, which is regulated by RLR signaling pathway. PMID:22412872

  3. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology

    PubMed Central

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2016-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins’ regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. PMID:26123302

  4. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.

    PubMed

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2015-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins' regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. © 2015 Elsevier Inc. All rights reserved.

  5. Regulation of Strigolactone Biosynthesis by Gibberellin Signaling1[OPEN

    PubMed Central

    Ito, Shinsaku; Yamagami, Daichi; Umehara, Mikihisa; Hanada, Atsushi; Sasaki, Yasuyuki; Yajima, Shunsuke; Kyozuka, Junko; Ueguchi-Tanaka, Miyako; Matsuoka, Makoto; Yamaguchi, Shinjiro

    2017-01-01

    Strigolactones (SLs) are a class of plant hormones that regulate diverse physiological processes, including shoot branching and root development. They also act as rhizosphere signaling molecules to stimulate the germination of root parasitic weeds and the branching of arbuscular mycorrhizal fungi. Although various types of cross talk between SLs and other hormones have been reported in physiological analyses, the cross talk between gibberellin (GA) and SLs is poorly understood. We screened for chemicals that regulate the level of SLs in rice (Oryza sativa) and identified GA as, to our knowledge, a novel SL-regulating molecule. The regulation of SL biosynthesis by GA is dependent on the GA receptor GID1 and F-box protein GID2. GA treatment also reduced the infection of rice plants by the parasitic plant witchers weed (Striga hermonthica). These data not only demonstrate, to our knowledge, the novel plant hormone cross talk between SL and GA, but also suggest that GA can be used to control parasitic weed infections. PMID:28404726

  6. Roles of chemical signals in regulation of the adaptive responses to iron deficiency.

    PubMed

    Liu, Xing Xing; He, Xiao Lin; Jin, Chong Wei

    2016-05-03

    Iron is an essential micronutrient for plants but is not readily accessible in most calcareous soils. Although the adaptive responses of plants to iron deficiency have been well documented, the signals involved in the regulatory cascade leading to their activation are not well understood to date. Recent studies revealed that chemical compounds, including sucrose, auxin, ethylene and nitric oxide, positively regulated the Fe-deficiency-induced Fe uptake processes in a cooperative manner. Nevertheless, cytokinins, jasmonate and abscisic acid were shown to act as negative signals in transmitting the iron deficiency information. The present mini review is to briefly address the roles of chemical signals in regulation of the adaptive responses to iron deficiency based on the literatures published in recent years.

  7. A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling

    PubMed Central

    Findlay, Greg M.; Yan, Lijun; Procter, Julia; Mieulet, Virginie; Lamb, Richard F.

    2007-01-01

    The mTOR (mammalian target of rapamycin) signalling pathway is a key regulator of cell growth and is controlled by growth factors and nutrients such as amino acids. Although signalling pathways from growth factor receptors to mTOR have been elucidated, the pathways mediating signalling by nutrients are poorly characterized. Through a screen for protein kinases active in the mTOR signalling pathway in Drosophila we have identified a Ste20 family member (MAP4K3) that is required for maximal S6K (S6 kinase)/4E-BP1 [eIF4E (eukaryotic initiation factor 4E)-binding protein 1] phosphorylation and regulates cell growth. Importantly, MAP4K3 activity is regulated by amino acids, but not the growth factor insulin and is not regulated by the mTORC1 inhibitor rapamycin. Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3. PMID:17253963

  8. Signaling threshold regulation by the Ras effector IMP.

    PubMed

    Matheny, Sharon A; White, Michael A

    2009-04-24

    The Ras effector and E3 ligase family member IMP (impedes mitogenic signal propagation) acts as a steady-state resistor within the Raf-MEK-ERK kinase module. IMP concentrations are directly regulated by Ras, through induction of autoubiquitination, to permit productive Raf-MEK complex assembly. Inhibition of Raf-MEK pathway activation by IMP occurs through the inactivation of KSR, a scaffold/adapter protein that couples activated Raf to its substrate MEK1. The capacity of IMP to inhibit signal propagation through Raf to MEK is, in part, a consequence of disrupting KSR1 homo-oligomerization and c-Raf-B-Raf hetero-oligomerization. These observations suggest that IMP functions as a threshold modulator, controlling sensitivity of the cascade to stimulus by directly limiting the assembly of functional KSR1-dependent Raf-MEK complexes.

  9. Calmodulin activity regulates group I metabotropic glutamate receptor-mediated signal transduction and synaptic depression.

    PubMed

    Sethna, Ferzin; Zhang, Ming; Kaphzan, Hanoch; Klann, Eric; Autio, Dawn; Cox, Charles L; Wang, Hongbing

    2016-05-01

    Group I metabotropic glutamate receptors (mGluR), including mGluR1 and mGluR 5 (mGluR1/5), are coupled to Gq and modulate activity-dependent synaptic plasticity. Direct activation of mGluR1/5 causes protein translation-dependent long-term depression (LTD). Although it has been established that intracellular Ca(2+) and the Gq-regulated signaling molecules are required for mGluR1/5 LTD, whether and how Ca(2+) regulates Gq signaling and upregulation of protein expression remain unknown. Through pharmacological inhibition, we tested the function of the Ca(2+) sensor calmodulin (CaM) in intracellular signaling triggered by the activation of mGluR1/5. CaM inhibitor N-[4-aminobutyl]-5-chloro-2-naphthalenesulfonamide hydrochloride (W13) suppressed the mGluR1/5-stimulated activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p70-S6 kinase 1 (S6K1) in hippocampal neurons. W13 also blocked the mGluR1/5 agonist-induced synaptic depression in hippocampal slices and in anesthetized mice. Consistent with the function of CaM, inhibiting the downstream targets Ca(2+) /CaM-dependent protein kinases (CaMK) blocked ERK1/2 and S6K1 activation. Furthermore, disruption of the CaM-CaMK-ERK1/2 signaling cascade suppressed the mGluR1/5-stimulated upregulation of Arc expression. Altogether, our data suggest CaM as a new Gq signaling component for coupling Ca(2+) and protein upregulation and regulating mGluR1/5-mediated synaptic modification. © 2016 Wiley Periodicals, Inc.

  10. E3 ubiquitin ligases: key regulators of hormone signaling in plants.

    PubMed

    Kelley, Dior

    2018-03-07

    Ubiquitin-mediated control of protein stability is central to most aspects of plant hormone signaling. Attachment of ubiquitin to target proteins occurs via an enzymatic cascade with the final step being catalyzed by a family of enzymes known as E3 ubiquitin ligases, which have been classified based on their protein domains and structures. While E3 ubiquitin ligases are conserved among eukaryotes, in plants they are well-known to fulfill unique roles as central regulators of phytohormone signaling, including hormone perception and regulation of hormone biosynthesis. This review will highlight up-to-date findings that have refined well-known E3 ligase-substrate interactions and defined novel E3 ligase substrates that mediate numerous hormone signaling pathways. Additionally, examples of how particular E3 ligases may mediate hormone crosstalk will be discussed as an emerging theme. Looking forward, promising experimental approaches and methods that will provide deeper mechanistic insight into the roles of E3 ubiquitin ligases in plants will be considered. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Regulation of T-cell receptor signalling by membrane microdomains

    PubMed Central

    Razzaq, Tahir M; Ozegbe, Patricia; Jury, Elizabeth C; Sembi, Phupinder; Blackwell, Nathan M; Kabouridis, Panagiotis S

    2004-01-01

    There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms. PMID:15554919

  12. Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein.

    PubMed

    Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

    2013-07-19

    RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

    PubMed Central

    Zeke, András; Misheva, Mariya

    2016-01-01

    SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. PMID:27466283

  14. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships.

    PubMed

    Zeke, András; Misheva, Mariya; Reményi, Attila; Bogoyevitch, Marie A

    2016-09-01

    The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. The cold response of CBF genes in barley is regulated by distinct signaling mechanisms.

    PubMed

    Marozsán-Tóth, Zsuzsa; Vashegyi, Ildikó; Galiba, Gábor; Tóth, Balázs

    2015-06-01

    Cold acclimation ability is crucial in the winter survival of cereals. In this process CBF transcription factors play key role, therefore understanding the regulation of these genes might provide useful knowledge for molecular breeding. In the present study the signal transduction pathways leading to the cold induction of different CBF genes were investigated in barley cv. Nure using pharmacological approach. Our results showed that the cold induced expression of CBF9 and CBF14 transcription factors is regulated by phospholipase C, phospholipase D pathways and calcium. On the contrary, these pathways have negative effect on the cold induction of CBF12 that is regulated by a different, as yet unidentified pathway. The diversity in the regulation of these transcription factors corresponds to their sequence based phylogenetic relationships suggesting that their evolutionary separation happened on structural, functional and regulational levels as well. On the CBF effector gene level, the signaling regulation is more complex, resultant effect of multiple pathways. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Negative Regulators of Insulin Signaling Revealed in a Genome-Wide Functional Screen

    PubMed Central

    Pitman, Jeffrey L.; Orth, Anthony P.; Gekakis, Nicholas

    2009-01-01

    Background Type 2 diabetes develops due to a combination of insulin resistance and β-cell failure and current therapeutics aim at both of these underlying causes. Several negative regulators of insulin signaling are known and are the subject of drug discovery efforts. We sought to identify novel contributors to insulin resistance and hence potentially novel targets for therapeutic intervention. Methodology An arrayed cDNA library encoding 18,441 human transcripts was screened for inhibitors of insulin signaling and revealed known inhibitors and numerous potential novel regulators. The novel hits included proteins of various functional classes such as kinases, phosphatases, transcription factors, and GTPase associated proteins. A series of secondary assays confirmed the relevance of the primary screen hits to insulin signaling and provided further insight into their modes of action. Conclusion/Significance Among the novel hits was PALD (KIAA1274, paladin), a previously uncharacterized protein that when overexpressed led to inhibition of insulin's ability to down regulate a FOXO1A-driven reporter gene, reduced upstream insulin-stimulated AKT phosphorylation, and decreased insulin receptor (IR) abundance. Conversely, knockdown of PALD gene expression resulted in increased IR abundance, enhanced insulin-stimulated AKT phosphorylation, and an improvement in insulin's ability to suppress FOXO1A-driven reporter gene activity. The present data demonstrate that the application of arrayed genome-wide screening technologies to insulin signaling is fruitful and is likely to reveal novel drug targets for insulin resistance and the metabolic syndrome. PMID:19727444

  17. CGI-58, a key regulator of lipid homeostasis and signaling in plants, also regulates polyamine metabolism

    USDA-ARS?s Scientific Manuscript database

    Comparative Gene Identification-58 (CGI-58) is an alpha/beta hydrolase-type protein that regulates lipid homeostasis and signaling in eukaryotes by interacting with and stimulating the activity of several different types of proteins, including a lipase in mammalian cells and a peroxisomal ABC transp...

  18. "The phactalysts": carbon nanotube/TiO2 composites as phototropic actuators for wireless remote triggering of chemical reactions and catalysis.

    PubMed

    Vassalini, Irene; Alessandri, Ivano

    2017-08-17

    A new concept of a reconfigurable smart catalyst was developed from the synergistic combination of polycarbonate/carbon nanotube bimorph photoactuators and TiO 2 . The addition of TiO 2 provides the photoactuators with photocatalytic activity and superior opto-mechanical properties, making phototropic actuation fast, reversible and responsive to Vis-NIR light sources. These composites were tested in the wireless, light-driven and spatially controlled remote triggering of different chemical reactions, including local explosions and photocatalytic polymerizations. The same materials were also investigated as efficient opto-mechanical shutters for the light-selective inhibition or activation of specific reactions, such as the photo-induced degradation of organic dyes. These results suggest that the integration of photocatalysts with soft photoactuators can open intriguing opportunities for chemistry and soft robotics.

  19. Regulation of Tissue Growth by the Mammalian Hippo Signaling Pathway

    PubMed Central

    Watt, Kevin I.; Harvey, Kieran F.; Gregorevic, Paul

    2017-01-01

    The integrative control of diverse biological processes such as proliferation, differentiation, apoptosis and metabolism is essential to maintain cellular and tissue homeostasis. Disruption of these underlie the development of many disease states including cancer and diabetes, as well as many of the complications that arise as a consequence of aging. These biological outputs are governed by many cellular signaling networks that function independently, and in concert, to convert changes in hormonal, mechanical and metabolic stimuli into alterations in gene expression. First identified in Drosophila melanogaster as a powerful mediator of cell division and apoptosis, the Hippo signaling pathway is a highly conserved regulator of mammalian organ size and functional capacity in both healthy and diseased tissues. Recent studies have implicated the pathway as an effector of diverse physiological cues demonstrating an essential role for the Hippo pathway as an integrative component of cellular homeostasis. In this review, we will: (a) outline the critical signaling elements that constitute the mammalian Hippo pathway, and how they function to regulate Hippo pathway-dependent gene expression and tissue growth, (b) discuss evidence that shows this pathway functions as an effector of diverse physiological stimuli and (c) highlight key questions in this developing field. PMID:29225579

  20. BMAL1-dependent regulation of the mTOR signaling pathway delays aging.

    PubMed

    Khapre, Rohini V; Kondratova, Anna A; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P; Kondratov, Roman V

    2014-01-01

    The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/- mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism.

  1. Matrix Rigidity Activates Wnt Signaling through Down-regulation of Dickkopf-1 Protein*

    PubMed Central

    Barbolina, Maria V.; Liu, Yiuying; Gurler, Hilal; Kim, Mijung; Kajdacsy-Balla, Andre A.; Rooper, Lisa; Shepard, Jaclyn; Weiss, Michael; Shea, Lonnie D.; Penzes, Peter; Ravosa, Matthew J.; Stack, M. Sharon

    2013-01-01

    Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear β-catenin and enhanced β-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling. PMID:23152495

  2. Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1 protein.

    PubMed

    Barbolina, Maria V; Liu, Yiuying; Gurler, Hilal; Kim, Mijung; Kajdacsy-Balla, Andre A; Rooper, Lisa; Shepard, Jaclyn; Weiss, Michael; Shea, Lonnie D; Penzes, Peter; Ravosa, Matthew J; Stack, M Sharon

    2013-01-04

    Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear β-catenin and enhanced β-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling.

  3. Enhanced gravi- and phototropism in plant mdr mutants mislocalizing the auxin efflux protein PIN1.

    PubMed

    Noh, Bosl; Bandyopadhyay, Anindita; Peer, Wendy Ann; Spalding, Edgar P; Murphy, Angus S

    2003-06-26

    Many aspects of plant growth and development are dependent on the flow of the hormone auxin down the plant from the growing shoot tip where it is synthesized. The direction of auxin transport in stems is believed to result from the basal localization within cells of the PIN1 membrane protein, which controls the efflux of the auxin anion. Mutations in two genes homologous to those encoding the P-glycoprotein ABC transporters that are especially abundant in multidrug-resistant tumour cells in animals were recently shown to block polar auxin transport in the hypocotyls of Arabidopsis seedlings. Here we show that the mdr mutants display faster and greater gravitropism and enhanced phototropism instead of the impaired curvature development expected in mutants lacking polar auxin transport. We find that these phenotypes result from a disruption of the normal accumulation of PIN1 protein along the basal end of hypocotyl cells associated with basipetal auxin flow. Lateral auxin conductance becomes relatively larger as a result, enhancing the growth differentials responsible for tropic responses.

  4. Intracellular antibody signalling is regulated by phosphorylation of the Fc receptor TRIM21

    PubMed Central

    Vaysburd, Marina; Yang, Ji-Chun; Mallery, Donna L; Zeng, Jingwei; Johnson, Christopher M; McLaughlin, Stephen H; Skehel, Mark; Maslen, Sarah; Cruickshank, James; Huguenin-Dezot, Nicolas; Chin, Jason W; Neuhaus, David

    2018-01-01

    Cell surface Fc receptors activate inflammation and are tightly controlled to prevent autoimmunity. Antibodies also simulate potent immune signalling from inside the cell via the cytosolic antibody receptor TRIM21, but how this is regulated is unknown. Here we show that TRIM21 signalling is constitutively repressed by its B-Box domain and activated by phosphorylation. The B-Box occupies an E2 binding site on the catalytic RING domain by mimicking E2-E3 interactions, inhibiting TRIM21 ubiquitination and preventing immune activation. TRIM21 is derepressed by IKKβ and TBK1 phosphorylation of an LxxIS motif in the RING domain, at the interface with the B-Box. Incorporation of phosphoserine or a phosphomimetic within this motif relieves B-Box inhibition, promoting E2 binding, RING catalysis, NF-κB activation and cytokine transcription upon infection with DNA or RNA viruses. These data explain how intracellular antibody signalling is regulated and reveal that the B-Box is a critical regulator of RING E3 ligase activity. PMID:29667579

  5. GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

    PubMed Central

    Jagasia, Ravi; Steib, Kathrin; Englberger, Elisabeth; Herold, Sabine; Faus-Kessler, Theresa; Saxe, Michael; Gage, Fred H.; Song, Hongjun; Lie, D. Chichung

    2009-01-01

    Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signalling pathways. Here, we investigate the role of CREB signalling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous fashion impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule associated protein, DCX, and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects following loss of GABA-mediated excitation can be compensated by enhanced CREB signalling. These results indicate that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation. PMID:19553437

  6. Growth patterns of the Cambrian microbialite: Phototropism and speciation of Epiphyton

    NASA Astrophysics Data System (ADS)

    Woo, J.; Chough, S. K.

    2010-07-01

    Microbes started constructing shallow marine stromatolitic bioherms in the Archean, but they transferred their role as a major buildup maker to metazoans in Phanerozoic. Microbial buildups often recovered their predominance in the carbonate platform when reefal metazoan communities collapsed. Epiphyton, an extinct taxon of calcified microbe that possessed branching filamentous trichomes, was an important reef builder in the shallow marine carbonate platform during Middle Cambrian, aftermath of an extinction of archaeocyath sponges which were major reef-building sessile organisms in the Early Cambrian. Here we present direct evidence of phototropism of Epiphyton, found from fossilized behavior in micro- and macro-structures of meter-scale microbial bioherms of the Zhangxia Formation (Middle Cambrian), North China Platform, Shandong Province, China. The bioherms consist of stacked growth layers with the inner and outer divisions divided by distinct boundary. The inner division of growth layers of the Epiphyton bioherm is dominated by dense uniform bush-shaped Epiphyton thalli, whereas the curved outer division has layered texture normal to the surface, comprised of elongated and chambered thalli. It suggests that photosynthetic Epiphyton reacted actively to the spatial changes in intensity of sunlight, controlled by angle of illumination on the curved growth surface of the bioherm. The inner and the outer divisions comprise different morpho-types of Epiphyton. The spatial distributions of different morpho-types in variously illuminated divisions of Epiphyton might have caused further speciation of Epiphyton.

  7. Regulator of G protein signaling 5 (RGS5) inhibits sonic hedgehog function in mouse cortical neurons.

    PubMed

    Liu, Chuanliang; Hu, Qiongqiong; Jing, Jia; Zhang, Yun; Jin, Jing; Zhang, Liulei; Mu, Lili; Liu, Yumei; Sun, Bo; Zhang, Tongshuai; Kong, Qingfei; Wang, Guangyou; Wang, Dandan; Zhang, Yao; Liu, Xijun; Zhao, Wei; Wang, Jinghua; Feng, Tao; Li, Hulun

    2017-09-01

    Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth. Here, we examined whether RGS5 regulates Shh signaling in neurons. RGS5 transcripts were found to be expressed in cortical neurons and their expression gradually declined in a time-dependent manner in culture system. When an adenovirus expressing RGS5 was introduced into an in vitro cell culture model of cortical neurons, RGS5 overexpression significantly reduced neurite outgrowth and FM4-64 uptake, while cAMP-PKA signaling was also affected. These findings suggest that RGS5 inhibits Shh function during neurite outgrowth and the presynaptic terminals of primary cortical neurons mature via modulation of cAMP. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3

    PubMed Central

    Cambier, Linda; Plate, Markus; Sucov, Henry M.; Pashmforoush, Mohammad

    2014-01-01

    A complex regulatory network of morphogens and transcription factors is essential for normal cardiac development. Nkx2-5 is among the earliest known markers of cardiac mesoderm that is central to the regulatory pathways mediating second heart field (SHF) development. Here, we have examined the specific requirements for Nkx2-5 in the SHF progenitors. We show that Nkx2-5 potentiates Wnt signaling by regulating the expression of the R-spondin3 (Rspo3) gene during cardiogenesis. R-spondins are secreted factors and potent Wnt agonists that in part regulate stem cell proliferation. Our data show that Rspo3 is markedly downregulated in Nkx2-5 mutants and that Rspo3 expression is regulated by Nkx2-5. Conditional inactivation of Rspo3 in the Isl1 lineage resulted in embryonic lethality secondary to impaired development of SHF. More importantly, we find that Wnt signaling is significantly attenuated in Nkx2-5 mutants and that enhancing Wnt/β-catenin signaling by pharmacological treatment or by transgenic expression of Rspo3 rescues the SHF defects in the conditional Nkx2-5+/− mutants. We have identified a previously unrecognized genetic link between Nkx2-5 and Wnt signaling that supports continued cardiac growth and proliferation during development. Identification of Rspo3 in cardiac development provides a new paradigm in temporal regulation of Wnt signaling by cardiac-specific transcription factors. PMID:25053429

  9. Notch signaling regulates the responses of lipopolysaccharide-stimulated macrophages in the presence of immune complexes.

    PubMed

    Wongchana, Wipawee; Kongkavitoon, Pornrat; Tangtanatakul, Pattarin; Sittplangkoon, Chutamath; Butta, Patcharavadee; Chawalitpong, Supatta; Pattarakankul, Thitiporn; Osborne, Barbara A; Palaga, Tanapat

    2018-01-01

    Macrophages exhibit diverse effector phenotypes depending on the stimuli and their microenvironment. Classically activated macrophages are primed with interferon (IFN)γ and stimulated with pathogen-associated molecular patterns. They produce inflammatory mediators and inflammatory cytokines, such as IL-12. In the presence of immune complexes (ICs), activated macrophages have decreased IL-12 production and increased IL-10 production and presumably act as regulatory macrophages. Notch signaling has been shown to regulate the effector functions of classically activated macrophages. In this study, we investigated whether Notch signaling is active in lipopolysaccharide (LPS)-stimulated macrophages in the presence of ICs. LPS/IC stimulation increased the level of cleaved Notch1 in murine macrophages, while IC stimulation alone did not. Delta-like 4, but not Jagged1, was responsible for generating cleaved Notch1. The activation of Notch signaling by LPS/ICs depended upon NF-κB and MEK/Erk pathway activation. Macrophages with the targeted deletion of Rbpj, which encodes a DNA-binding protein central to canonical Notch signaling, produced significantly less IL-10 upon LPS/IC stimulation. A similar impact on IL-10 production was observed when Notch signaling was inhibited with a gamma-secretase inhibitor (GSI). Defects in NF-κB p50 nuclear localization were observed in GSI-treated macrophages and in Rbpj-/- macrophages, suggesting cross-regulation between the Notch and NF-κB pathways. Transcriptomic analysis revealed that Notch signaling regulates the transcription of genes involved in the cell cycle, macrophage activation, leukocyte migration and cytokine production in LPS/IC-stimulated macrophages. Taken together, these results suggest that the Notch signaling pathway plays an important role in regulating the functions of macrophages activated by LPS and ICs.

  10. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein.

    PubMed

    Stroschein, S L; Wang, W; Zhou, S; Zhou, Q; Luo, K

    1999-10-22

    Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR. Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target genes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-beta-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling.

  11. Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

    PubMed Central

    Levin, David E.

    2011-01-01

    The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. PMID:22174182

  12. Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium

    PubMed Central

    Delos Santos, Ralph Christian; Bautista, Stephen; Lucarelli, Stefanie; Bone, Leslie N.; Dayam, Roya M.; Abousawan, John; Botelho, Roberto J.; Antonescu, Costin N.

    2017-01-01

    Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question. We examined the selective regulation of clathrin-dependent EGFR signaling and endocytosis. We find that perturbations of phospholipase Cγ1 (PLCγ1), Ca2+, or protein kinase C (PKC) impair clathrin-mediated endocytosis of EGFR, the formation of CCPs harboring EGFR, and EGFR signaling. Each of these manipulations was without effect on the clathrin-mediated endocytosis of transferrin receptor (TfR). EGFR and TfR were recruited to largely distinct clathrin structures. In addition to control of initiation and assembly of CCPs, EGF stimulation also elicited a Ca2+- and PKC-dependent reduction in synaptojanin1 recruitment to clathrin structures, indicating broad control of CCP assembly by Ca2+ signals. Hence EGFR elicits PLCγ1-calcium signals to facilitate formation of a subset of CCPs, thus modulating its own signaling and endocytosis. This provides evidence for the versatility of CCPs to control diverse cellular processes. PMID:28814502

  13. Epidermal wound repair is regulated by the planar cell polarity signaling pathway.

    PubMed

    Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A; Murdoch, Jennifer N; Humbert, Patrick O; Parekh, Vishwas; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M; Jane, Stephen M

    2010-07-20

    The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3(-)(/-) mice, we identified RhoGEF19, a homolog of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerization, cellular polarity, and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling and broadly implicate this pathway in epidermal repair. (c) 2010 Elsevier Inc. All rights reserved.

  14. Epidermal wound repair is regulated by the planar cell polarity signaling pathway

    PubMed Central

    Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B.; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A.; Murdoch, Jennifer N.; Humbert, Patrick O.; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M.; Jane, Stephen M.

    2010-01-01

    SUMMARY The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3−/− mice, we identified RhoGEF19, a homologue of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerisation, cellular polarity and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling, and broadly implicate this pathway in epidermal repair. PMID:20643356

  15. Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila

    PubMed Central

    Bai, Hua; Kang, Ping; Hernandez, Ana Maria; Tatar, Marc

    2013-01-01

    Reduced insulin/IGF signaling increases lifespan in many animals. To understand how insulin/IGF mediates lifespan in Drosophila, we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin/IGF signaling genotypes. Dawdle, an Activin ligand, is bound and repressed by dFOXO when reduced insulin/IGF extends lifespan. Reduced Activin signaling improves performance and protein homeostasis in muscles of aged flies. Activin signaling through the Smad binding element inhibits the transcription of Autophagy-specific gene 8a (Atg8a) within muscle, a factor controlling the rate of autophagy. Expression of Atg8a within muscle is sufficient to increase lifespan. These data reveal how insulin signaling can regulate aging through control of Activin signaling that in turn controls autophagy, representing a potentially conserved molecular basis for longevity assurance. While reduced Activin within muscle autonomously retards functional aging of this tissue, these effects in muscle also reduce secretion of insulin-like peptides at a distance from the brain. Reduced insulin secretion from the brain may subsequently reinforce longevity assurance through decreased systemic insulin/IGF signaling. PMID:24244197

  16. Testosterone regulation of Akt/mTORC1/FoxO3a Signaling in Skeletal Muscle

    PubMed Central

    White, James P.; Gao, Song; Puppa, Melissa J.; Sato, Shuichi; Welle, Stephen L.; Carson, James A.

    2012-01-01

    Low endogenous testosterone production, known as hypogonadism is commonly associated with conditions inducing muscle wasting. Akt signaling can control skeletal muscle mass through mTOR regulation of protein synthesis and FoxO regulation of protein degradation, and this pathway has been previously identified as a target of androgen signaling. However, the testosterone sensitivity of Akt/mTOR signaling requires further understanding in order to grasp the significance of varied testosterone levels seen with wasting disease on muscle protein turnover regulation. Therefore, the purpose of this study is to determine the effect of androgen availability on muscle Akt/mTORC1/FoxO3a regulation in skeletal muscle and cultured C2C12 myotubes. C57BL/6 mice were either castrated for 42 days or castrated and treated with the nandrolone decanoate (ND) (6 mg/kg bw/wk). Testosterone loss (TL) significantly decreased volitional grip strength, body weight, and gastrocnemius (GAS) muscle mass, and ND reversed these changes. Related to muscle mass regulation, TL decreased muscle IGF-1 mRNA, the rate of myofibrillar protein synthesis, Akt phosphorylation, and the phosphorylation of Akt targets, GSK3β, PRAS40 and FoxO3a. TL induced expression of FoxO transcriptional targets, MuRF1, atrogin1 and REDD1. Muscle AMPK and raptor phosphorylation, mTOR inhibitors, were not altered by low testosterone. ND restored IGF-1 expression and Akt/mTORC1 signaling while repressing expression of FoxO transcriptional targets. Testosterone (T) sensitivity of Akt/mTORC1 signaling was examined in C2C12 myotubes, and mTOR phosphorylation was induced independent of Akt activation at low T concentrations, while a higher T concentration was required to activate Akt signaling. Interestingly, low concentration T was sufficient to amplify myotube mTOR and Akt signaling after 24h of T withdrawal, demonstrating the potential in cultured myotubes for a T initiated positive feedback mechanism to amplify Akt

  17. IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation

    PubMed Central

    Natarajan, Vivek T.; Ganju, Parul; Singh, Archana; Vijayan, Vinaya; Kirty, Kritika; Yadav, Shalini; Puntambekar, Shraddha; Bajaj, Sonali; Dani, Prachi P.; Kar, Hemanta K.; Gadgil, Chetan J.; Natarajan, Krishnamurthy; Rani, Rajni; Gokhale, Rajesh S.

    2014-01-01

    Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigmentation biology. We show that IFN-γ signaling impedes maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. Withdrawal of IFN-γ signal spontaneously restores normal cellular programming. This effect in melanocytes is mediated by IFN regulatory factor-1 and is not dependent on the central regulator microphthalmia-associated transcription factor. Chronic IFN-γ signaling shows a clear hypopigmentation phenotype in both mouse and human skin. Interestingly, IFN-γ KO mice display a delayed recovery response to restore basal state of epidermal pigmentation after UV-induced tanning. Together, our studies delineate a new spatiotemporal role of the IFN-γ signaling network in skin pigmentation homeostasis, which could have implications in various cutaneous depigmentary and malignant disorders. PMID:24474804

  18. Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

    PubMed Central

    Gur-Cohen, Shiri; Kollet, Orit; Graf, Claudine; Esmon, Charles T.; Ruf, Wolfram; Lapidot, Tsvee

    2016-01-01

    The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/PAR1 signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR+ LT-HSC BM retention and egress. EPCR/PAR1 signaling facilitates LT-HSC BM repopulation, retention, survival, and chemotherapy resistance by restricting nitric oxide (NO) production, maintaining NOlow LT-HSC BM retention with increased VLA4 expression, affinity, and adhesion. Conversely, acute stress and clinical mobilization upregulate thrombin generation and activate different PAR1 signaling which overcomes BM EPCR+ LT-HSC retention, inducing their recruitment to the bloodstream. Thrombin/PAR1 signaling induces NO generation, TACE-mediated EPCR shedding, and upregulation of CXCR4 and PAR1, leading to CXCL12-mediated stem and progenitor cell mobilization. This review discusses new roles for factors traditionally viewed as coagulation related, which independently act in the BM to regulate PAR1 signaling in bone- and blood-forming progenitor cells, navigating their fate by controlling NO production. PMID:26928241

  19. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling1[OPEN

    PubMed Central

    2016-01-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. PMID:27208308

  20. Ground-based studies of tropisms in hardware developed for the European Modular Cultivation System (EMCS)

    NASA Astrophysics Data System (ADS)

    Correll, Melanie J.; Edelmann, Richard E.; Hangarter, Roger P.; Mullen, Jack L.; Kiss, John Z.

    Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μg, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station, we have been conducting ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments with Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue- and red-light signaling systems interact with each other and with the gravisensing system.

  1. Spaceflight studies of tropisms in the European Modular Cultivation System

    NASA Astrophysics Data System (ADS)

    Kiss, J. Z.; Correll, M. J.; Edelmann, R. E.

    Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μ g, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station (ISS), we have been performing ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments that will use Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue-light and red-light signaling systems interact with each other, and also with the gravisensing system.

  2. Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis.

    PubMed

    Hill, Jennifer W; Xu, Yong; Preitner, Frederic; Fukuda, Makota; Cho, You-Ree; Luo, Ji; Balthasar, Nina; Coppari, Roberto; Cantley, Lewis C; Kahn, Barbara B; Zhao, Jean J; Elmquist, Joel K

    2009-11-01

    Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis.

  3. JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling

    PubMed Central

    Recasens-Alvarez, Carles; Ferreira, Ana; Milán, Marco

    2017-01-01

    A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. Here we present evidence that JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage. We identify the inhibitor of apoptosis dIAP1 and Cyclin A as two critical genes regulated by JAK/STAT and contributing to the growth of the Hedgehog-expressing cell population. We also unravel an early role of JAK/STAT in guaranteeing Wingless-mediated appendage specification, and a later one in restricting the Dpp-organizing activity to the appendage itself. These results unveil a fundamental role of the conserved JAK/STAT pathway in limb specification and growth by regulating morphogen production and signalling, and a function of pro-survival cues and mitogenic signals in the regulation of the pool of morphogen-producing cells in a developing organ. PMID:28045022

  4. PTEN, a negative regulator of PI3K/Akt signaling, sustains brain stem cardiovascular regulation during mevinphos intoxication.

    PubMed

    Tsai, Ching-Yi; Wu, Jacqueline C C; Fang, Chi; Chang, Alice Y W

    2017-09-01

    Activation of PI3K/Akt signaling, leading to upregulation of nitric oxide synthase II (NOS II)/peroxynitrite cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins cardiovascular depression induced by the organophosphate pesticide mevinphos. By exhibiting dual-specificity protein- and lipid-phosphatase activity, phosphatase and tensin homolog (PTEN) directly antagonizes the PI3K/Akt signaling by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate, the lipid product of PI3K. Based on the guiding hypothesis that PTEN may sustain brain stem cardiovascular regulation during mevinphos intoxication as a negative regulator of PI3K/Akt signaling in the RVLM, we aimed in this study to clarify the mechanistic role of PTEN in mevinphos-induced circulatory depression. Microinjection bilaterally of mevinphos (10 nmol) into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension and a decrease in baroreflex-mediated sympathetic vasomotor tone. There was progressive augmentation in PTEN activity as reflected by a decrease in the oxidized form of PTEN in the RVLM during mevinhpos intoxication, without significant changes in the mRNA or protein level of PTEN. Loss-of-function manipulations of PTEN in the RVLM by immunoneutralization, pharmacological blockade or siRNA pretreatment significantly potentiated the increase in Akt activity or NOS II/peroxynitrite cascade in the RVLM, enhanced the elicited hypotension and exacerbated the already reduced baroreflex-mediated sympathetic vasomotor tone. We conclude that augmented PTEN activity via a decrease of its oxidized form in the RVLM sustains brain stem cardiovascular regulation during mevinphos intoxication via downregulation of the NOS II/peroxynitrite cascade as a negative regulator of PI3K/Akt signaling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Regulation of a hitchhiking behavior by neuronal insulin and TGF-β signaling in the nematode Caenorhabditis elegans.

    PubMed

    Lee, Daehan; Lee, Harksun; Kim, Nari; Lim, Daisy S; Lee, Junho

    2017-03-04

    Free-living nematode Caenorhabditis elegans exhibits various behaviors to adapt to the fluctuating environment. When early larvae of C. elegans experience the harsh environmental condition, they develop to an alternative developmental stage called dauer, which shows nictation, a stage-specific waving behavior. Nictation enables dauers to attach to more mobile animals, which helps them disperse to other habitats beyond physical barriers. However, underlying molecular mechanisms that regulate nictation behavior are largely unknown. In this study, we show that insulin signaling and transforming growth beta (TGF-β) signaling, the two major parallel signaling pathways that mediate dauer development, are involved in the regulation of dauer-specific nictation behavior. Genetic analysis revealed that downregulation of insulin signaling enhanced nictation behavior. Heat-shock induced rescue experiments showed that the action period of the insulin signaling is before dauer formation. Surprisingly, lowering of TGF-β signaling inhibited the normal performance of nictation, suggesting that TGF-β signaling acts in an opposite way from that for dauer formation. Cell-specific rescue experiments revealed that two signaling pathways act in the nervous system and an epistasis experiment showed that TGF-β signaling is epistatic to insulin signaling. Taken together, we propose that the neuroendocrinal insulin signaling and TGF-β signaling regulate nictation behavior during development in response to environmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Identification of critical paralog groups with indispensable roles in the regulation of signaling flow

    PubMed Central

    Modos, Dezso; Brooks, Johanne; Fazekas, David; Ari, Eszter; Vellai, Tibor; Csermely, Peter; Korcsmaros, Tamas; Lenti, Katalin

    2016-01-01

    Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and ‘bowtieness’ when compared to other paralogs or other proteins in the signaling network. CPGs had higher diversity in all these measures, with more varied biological functions and more specific post-transcriptional regulation than non-critical paralog groups (non-CPG). Using TGF-beta, Notch and MAPK pathways as examples, SMAD2/3, NOTCH1/2/3 and MEK3/6-p38 CPGs were found to regulate the signaling flow of their respective pathways. Additionally, CPGs showed a higher mutation rate in both inherited diseases and cancer, and were enriched in drug targets. In conclusion, the results revealed two distinct types of paralog groups in the signaling network: CPGs and non-CPGs. Thus highlighting the importance of CPGs as compared to non-CPGs in drug discovery and disease pathogenesis. PMID:27922122

  7. BMAL1-dependent regulation of the mTOR signaling pathway delays aging

    PubMed Central

    Khapre, Rohini V.; Kondratova, Anna A.; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P.; Kondratov, Roman V.

    2014-01-01

    The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1−/− mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism. PMID:24481314

  8. Regulation and signaling of human bombesin receptors and their biological effects.

    PubMed

    Weber, H Christian

    2009-02-01

    This review will highlight recent advances in the understanding of molecular mechanisms by which mammalian bombesin receptors are regulated and which intracellular signaling pathways have been characterized to mediate agonist-dependent receptor biological effects. Mammalian bombesin receptors have been demonstrated to be involved in a larger array of physiological and pathophysiological conditions than previously reported. Pharmacological experiments in vitro and in vivo as well as utilization of animals genetically deficient of the gastrin-releasing peptide receptor demonstrated roles in memory and fear behavior, lung development and injury, small intestinal cell repair, autocrine tumor growth, and mediating signals for pruritus and penile reflexes. Intracellular signaling studies predominantly of the gastrin-releasing peptide receptor owing to its frequent overexpression in some human malignancies showed that PI3 kinase activation is an important mechanism of cell proliferation. Tumor cell treatment including gastrin-releasing peptide receptor antagonists combined with inhibition of epidermal growth factor receptor resulted in an additive effect on blocking cell proliferation. Novel molecular mechanisms of the orphan bombesin receptor subtype-3 and gastrin-releasing peptide receptor gene regulation have been elucidated. Inhibition of gastrin-releasing peptide receptor signaling in human malignancies represents an attractive target for pharmacological treatment. Novel functions of bombesin related peptides have been identified including processes in the central nervous system, lung and intestinal tract.

  9. RNF11 is a multifunctional modulator of growth factor receptor signalling and transcriptional regulation.

    PubMed

    Azmi, Peter; Seth, Arun

    2005-11-01

    Our laboratory has found that the 154aa RING finger protein 11 (RNF11), has modular domains and motifs including a RING-H2 finger domain, a PY motif, an ubiquitin interacting motif (UIM), a 14-3-3 binding sequence and an AKT phosphorylation site. RNF11 represents a unique protein with no other known immediate family members yet described. Comparative genetic analysis has shown that RNF11 is highly conserved throughout evolution. This may indicate a conserved and non-redundant role for the RNF11 protein. Molecular binding assays using RNF11 have shown that RNF11 has important roles in growth factor signalling, ubiquitination and transcriptional regulation. RNF11 has been shown to interact with HECT-type E3 ubiquitin ligases Nedd4, AIP4, Smurf1 and Smurf2, as well as with Cullin1, the core protein in the multi-subunit SCF E3 ubiquitin ligase complex. Work done in our laboratory has shown that RNF11 is capable of antagonizing Smurf2-mediated inhibition of TGFbeta signalling. Furthermore, RNF11 is capable of degrading AMSH, a positive regulator of both TGFbeta and EGFR signalling pathways. Recently, we have found that RNF11 can directly enhance TGFbeta signalling through a direct association with Smad4, the common signal transducer and transcription factor in the TGFbeta, BMP, and Activin pathways. Through its association with Smad4 and other transcription factors, RNF11 may have a role in direct transcriptional regulation. Our laboratory and others have found nearly 80 protein interactions for RNF11, placing RNF11 at the cross-roads of cell signalling and transcriptional regulation. RNF11 is highly expressed in breast tumours. Deregulation of RNF11 function may prove to be harmful to patient therapeutic outcomes. RNF11 may therefore provide a novel target for cancer therapeutics. The purpose of this review is to discuss the role of RNF11 in cell signalling and transcription factor modulation with special attention given to the ubiquitin-proteasomal pathway, TGFbeta

  10. MEKK4 Signaling Regulates Sensory Cell Development and Function in the Mouse Inner Ear

    PubMed Central

    Haque, Khujista; Pandey, Atul K.; Zheng, Hong-Wei; Riazuddin, Saima; Sha, Su-Hua

    2016-01-01

    Mechanosensory hair cells (HCs) residing in the inner ear are critical for hearing and balance. Precise coordination of proliferation, sensory specification, and differentiation during development is essential to ensure the correct patterning of HCs in the cochlear and vestibular epithelium. Recent studies have revealed that FGF20 signaling is vital for proper HC differentiation. However, the mechanisms by which FGF20 signaling promotes HC differentiation remain unknown. Here, we show that mitogen-activated protein 3 kinase 4 (MEKK4) expression is highly regulated during inner ear development and is critical to normal cytoarchitecture and function. Mice homozygous for a kinase-inactive MEKK4 mutation exhibit significant hearing loss. Lack of MEKK4 activity in vivo also leads to a significant reduction in the number of cochlear and vestibular HCs, suggesting that MEKK4 activity is essential for overall development of HCs within the inner ear. Furthermore, we show that loss of FGF20 signaling in vivo inhibits MEKK4 activity, whereas gain of Fgf20 function stimulates MEKK4 expression, suggesting that Fgf20 modulates MEKK4 activity to regulate cellular differentiation. Finally, we demonstrate, for the first time, that MEKK4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence HC development and that FGFR1 signaling through activation of MEKK4 is necessary for outer hair cell differentiation. Collectively, this study provides compelling evidence of an essential role for MEKK4 in inner ear morphogenesis and identifies the requirement of MEKK4 expression in regulating the specific response of FGFR1 during HC development and FGF20/FGFR1 signaling activated MEKK4 for normal sensory cell differentiation. SIGNIFICANCE STATEMENT Sensory hair cells (HCs) are the mechanoreceptors within the inner ear responsible for our sense of hearing. HCs are formed before birth, and mammals lack the ability to restore the sensory deficits associated

  11. JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium.

    PubMed

    Gomi, Kazunori; Staudt, Michelle R; Salit, Jacqueline; Kaner, Robert J; Heldrich, Jonna; Rogalski, Allison M; Arbelaez, Vanessa; Crystal, Ronald G; Walters, Matthew S

    2016-08-01

    Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process in the human airway epithelium is largely unknown. The objective of this study was to define the role of the Notch ligand JAG1 in regulating human BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. These data demonstrate JAG1-mediated Notch signaling regulates differentiation of BC into secretory cells.

  12. Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

    PubMed Central

    Grimes, William N.; Zhang, Jun; Tian, Hua; Graydon, Cole W.; Hoon, Mrinalini; Rieke, Fred

    2015-01-01

    Neuronal microcircuits, small, localized signaling motifs involving two or more neurons, underlie signal processing and computation in the brain. Compartmentalized signaling within a neuron may enable it to participate in multiple, independent microcircuits. Each A17 amacrine cell in the mammalian retina contains within its dendrites hundreds of synaptic feedback microcircuits that operate independently to modulate feedforward signaling in the inner retina. Each of these microcircuits comprises a small (<1 μm) synaptic varicosity that typically receives one excitatory synapse from a presynaptic rod bipolar cell (RBC) and returns two reciprocal inhibitory synapses back onto the same RBC terminal. Feedback inhibition from the A17 sculpts the feedforward signal from the RBC to the AII, a critical component of the circuitry mediating night vision. Here, we show that the two inhibitory synapses from the A17 to the RBC express kinetically distinct populations of GABA receptors: rapidly activating GABAARs are enriched at one synapse while more slowly activating GABACRs are enriched at the other. Anatomical and electrophysiological data suggest that macromolecular complexes of voltage-gated (Cav) channels and Ca2+-activated K+ channels help to regulate GABA release from A17 varicosities and limit GABACR activation under certain conditions. Finally, we find that selective elimination of A17-mediated feedback inhibition reduces the signal to noise ratio of responses to dim flashes recorded in the feedforward pathway (i.e., the AII amacrine cell). We conclude that A17-mediated feedback inhibition improves the signal to noise ratio of RBC-AII transmission near visual threshold, thereby improving visual sensitivity at night. PMID:25972578

  13. sNASP inhibits TLR signaling to regulate immune response in sepsis.

    PubMed

    Yang, Feng-Ming; Zuo, Yong; Zhou, Wei; Xia, Chuan; Hahm, Bumsuk; Sullivan, Mark; Cheng, Jinke; Chang, Hui-Ming; Yeh, Edward Th

    2018-06-01

    Many Toll-like receptors (TLRs) signal through TNF receptor-associated factor 6 (TRAF6) to activate innate immune responses. Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. In sNasp S158A knockin (S158A-KI) mice, LPS-treated macrophages could not phosphorylate sNASP, which remained bound to TRAF6. S158A-KI mice were more susceptible to sepsis due to a marked reduction in IL-1β, TNF-α, and IFN-γ production accompanied by an inability to clear bacteria and recruit leukocytes. Furthermore, phosphorylation-regulated release of sNASP from TRAF6 is observed following activation of TLR-1, -2, -4, -5, and -6. Thus, sNASP is a negative regulator of TLR signaling to modulate the innate immune response.

  14. Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

    PubMed

    Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

    2018-05-16

    Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

  15. Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

    PubMed Central

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer. PMID:25786122

  16. Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

    PubMed

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

  17. Rho-associated protein kinase regulates subcellular localisation of Angiomotin and Hippo-signalling during preimplantation mouse embryo development.

    PubMed

    Mihajlović, Aleksandar I; Bruce, Alexander W

    2016-09-01

    The differential activity of the Hippo-signalling pathway between the outer- and inner-cell populations of the developing preimplantation mouse embryo directs appropriate formation of trophectoderm and inner cell mass (ICM) lineages. Such distinct signalling activity is under control of intracellular polarization, whereby Hippo-signalling is either supressed in polarized outer cells or activated in apolar inner cells. The central role of apical-basolateral polarization to such differential Hippo-signalling regulation prompted us to reinvestigate the role of potential upstream molecular regulators affecting apical-basolateral polarity. This study reports that the chemical inhibition of Rho-associated kinase (Rock) is associated with failure to form morphologically distinct blastocysts, indicative of compromised trophectoderm differentiation, and defects in the localization of both apical and basolateral polarity factors associated with malformation of tight junctions. Moreover, Rock-inhibition mediates mislocalization of the Hippo-signalling activator Angiomotin (Amot), to the basolateral regions of outer cells and is concomitant with aberrant activation of the pathway. The Rock-inhibition phenotype is mediated by Amot, as RNAi-based Amot knockdown totally rescues the normal suppression of Hippo-signalling in outer cells. In conclusion, Rock, via regulating appropriate apical-basolateral polarization in outer cells, regulates the appropriate activity of the Hippo-signalling pathway, by ensuring correct subcellular localization of Amot protein in outer cells. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3.

    PubMed

    Cambier, Linda; Plate, Markus; Sucov, Henry M; Pashmforoush, Mohammad

    2014-08-01

    A complex regulatory network of morphogens and transcription factors is essential for normal cardiac development. Nkx2-5 is among the earliest known markers of cardiac mesoderm that is central to the regulatory pathways mediating second heart field (SHF) development. Here, we have examined the specific requirements for Nkx2-5 in the SHF progenitors. We show that Nkx2-5 potentiates Wnt signaling by regulating the expression of the R-spondin3 (Rspo3) gene during cardiogenesis. R-spondins are secreted factors and potent Wnt agonists that in part regulate stem cell proliferation. Our data show that Rspo3 is markedly downregulated in Nkx2-5 mutants and that Rspo3 expression is regulated by Nkx2-5. Conditional inactivation of Rspo3 in the Isl1 lineage resulted in embryonic lethality secondary to impaired development of SHF. More importantly, we find that Wnt signaling is significantly attenuated in Nkx2-5 mutants and that enhancing Wnt/β-catenin signaling by pharmacological treatment or by transgenic expression of Rspo3 rescues the SHF defects in the conditional Nkx2-5(+/-) mutants. We have identified a previously unrecognized genetic link between Nkx2-5 and Wnt signaling that supports continued cardiac growth and proliferation during development. Identification of Rspo3 in cardiac development provides a new paradigm in temporal regulation of Wnt signaling by cardiac-specific transcription factors. © 2014. Published by The Company of Biologists Ltd.

  19. SCF(KMD) controls cytokinin signaling by regulating the degradation of type-B response regulators.

    PubMed

    Kim, Hyo Jung; Chiang, Yi-Hsuan; Kieber, Joseph J; Schaller, G Eric

    2013-06-11

    Cytokinins are plant hormones that play critical roles in growth and development. In Arabidopsis, the transcriptional response to cytokinin is regulated by action of type-B Arabidopsis response regulators (ARRs). Although central elements in the cytokinin signal transduction pathway have been identified, mechanisms controlling output remain to be elucidated. Here we demonstrate that a family of F-box proteins, called the kiss me deadly (KMD) family, targets type-B ARR proteins for degradation. KMD proteins form an S-phase kinase-associated PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins. Loss-of-function KMD mutants stabilize type-B ARRs and exhibit an enhanced cytokinin response. In contrast, plants with elevated KMD expression destabilize type-B ARR proteins leading to cytokinin insensitivity. Our results support a model in which an SCF(KMD) complex negatively regulates cytokinin responses by controlling levels of a key family of transcription factors.

  20. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae

    PubMed Central

    Kato, Michiko; Lin, Su-Ju

    2014-01-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD+ is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD+ homeostasis is essential for proper cellular function and aberrant NAD+ metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD+ metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD+ metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD+ metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD+ metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD+ metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD+-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD+ intermediates, and their potential roles in NAD+ homeostasis. To date, it remains unclear how NAD+ and NAD+ intermediates shuttle between different

  1. Producing the Ethylene Signal: Regulation and Diversification of Ethylene Biosynthetic Enzymes1

    PubMed Central

    Booker, Matthew A.; DeLong, Alison

    2015-01-01

    Strictly controlled production of ethylene gas lies upstream of the signaling activities of this crucial regulator throughout the plant life cycle. Although the biosynthetic pathway is enzymatically simple, the regulatory circuits that modulate signal production are fine tuned to allow integration of responses to environmental and intrinsic cues. Recently identified posttranslational mechanisms that control ethylene production converge on one family of biosynthetic enzymes and overlay several independent reversible phosphorylation events and distinct mediators of ubiquitin-dependent protein degradation. Although the core pathway is conserved throughout seed plants, these posttranslational regulatory mechanisms may represent evolutionarily recent innovations. The evolutionary origins of the pathway and its regulators are not yet clear; outside the seed plants, numerous biochemical and phylogenetic questions remain to be addressed. PMID:26134162

  2. SMAD4 feedback regulates the canonical TGF-β signaling pathway to control granulosa cell apoptosis.

    PubMed

    Du, Xing; Pan, Zengxiang; Li, Qiqi; Liu, Honglin; Li, Qifa

    2018-02-02

    Canonical TGF-β signals are transduced from the cell surface to the cytoplasm, and then translocated into the nucleus, a process that involves ligands (TGF-β1), receptors (TGFBR2/1), receptor-activated SMADs (SMAD2/3), and the common SMAD (SMAD4). Here we provide evidence that SMAD4, a core component of the canonical TGF-β signaling pathway, regulates the canonical TGF-β signaling pathway in porcine granulosa cells (GCs) through a feedback mechanism. Genome-wide analysis and qRT-PCR revealed that SMAD4 affected miRNA biogenesis in GCs. Interestingly, TGFBR2, the type II receptor of the canonical TGF-β signaling pathway, was downregulated in SMAD4-silenced GCs and found to be a common target of SMAD4-inhibited miRNAs. miR-425, the most significantly elevated miRNA in SMAD4-silenced GCs, mediated the SMAD4 feedback regulation of the TGF-β signaling pathway. This was accomplished through a direct interaction between the transcription factor SMAD4 and the miR-425 promoter, and a direct interaction between miR-425 and the TGFBR2 3'-UTR. Furthermore, miR-425 enhanced GC apoptosis by targeting TGFBR2 and the canonical TGF-β signaling pathway, which was rescued by SMAD4 and TGF-β1. Overall, our findings demonstrate that a positive feedback mechanism exists within the canonical TGF-β signaling pathway. This study also provides new insights into mechanism underlying the canonical TGF-β signaling pathway, which regulates GC function and follicular development.

  3. Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells.

    PubMed

    Fan, Hong; Paiboonrungruan, Chorlada; Zhang, Xinyan; Prigge, Justin R; Schmidt, Edward E; Sun, Zheng; Chen, Xiaoxin

    2017-11-04

    Oxidative stress is known to play a pivotal role in the development of oral squamous cell carcinoma (OSCC). We have demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has chemopreventive effects against oxidative stress-associated OSCC. However, Nrf2 have dual roles in cancer development; while it prevents carcinogenesis of normal cells, hyperactive Nrf2 also promotes the survival of cancer cells. This study is aimed to understand the function of Nrf2 in regulating cellular behaviors of OSCC cells, and the potential mechanisms through which Nrf2 facilitates OSCC. We established the Nrf2-overexpressing and Nrf2-knockdown OSCC cell lines, and examined the function of Nrf2 in regulating cell proliferation, migration, invasion, cell cycle and colony formation. Our data showed that Nrf2 overexpression promoted cancer phenotypes in OSCC cells, whereas Nrf2 silencing inhibited these phenotypes. In addition, Nrf2 positively regulated Notch signaling pathway in OSCC cells in vitro. Consistent with this observation, Nrf2 activation in Keap1 -/- mice resulted in not only hyperproliferation of squamous epithelial cells in mouse tongue as evidenced by increased expression of PCNA, but also activation of Notch signaling in these cells as evidenced by increased expression of NICD1 and Hes1. In conclusion, Nrf2 regulates cancer behaviors and Notch signaling in OSCC cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Osteogenic Transcription Regulated by Exaggerated Stretch Loading via Convergent Wnt Signaling

    NASA Technical Reports Server (NTRS)

    Juran, Cassandra M.; Blaber, Elizabeth A.; Almeida, Eduardo A. C.

    2017-01-01

    Cell and animal studies conducted onboard the International Space Station and formerly the Shuttle flights have provided data illuminating the deleterious biological response of bone to mechanical unloading. Down regulation of proliferative mechanisms within stem cell populations of the osteogenic niche is a suggested mechanism for loss of bone mass. However the intercellular communicative cues from osteoblasts and osteocytes in managing stem cell proliferation and osteogenic differentiation are largely unknown. In this investigation, MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells, are co-culture under dynamic tensile conditions and evaluated for phenotypic expression of biochemical signaling proteins influential in driving stem cell differentiation. MLO-Y4 and MC3T3-E1 were co-cultured on polyethersulfone membrane with a 0.45m porosity to permit soluble factor transfer and direct cell-cell gap junction signaling. Cyclic tensile stimulation was applied for 48 h at a frequency of 0.1Hz and strain of 0.1. Total Live cell counts indicate mechanical activation of MC3T3-E1s inhibits proliferation while MLO-Y4s increase in number. However, the percent of live MLO-Y4s within the population is low (46.3 total count, *p0.05, n4) suggesting a potential apoptotic signaling cascade. Immunofluorescence demonstrated that stimulation of co-cultures elicits increased gap junction communication. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggest that an osteocyte-osteoblast signaling feedback mechanism may regulate mechanotransduction of an apoptotic cascade within osteocytes and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

  5. Role of IKK-alpha in the EGFR Signaling Regulation

    DTIC Science & Technology

    2014-09-01

    Rho family GTPase (VAV2), and Phospholipase C (PLC) (4). These signaling activities regulate cell proliferation, mobility , and differentiation in...correlation coefficient r=0.63, pɘ.05) was found, suggesting that high IKK promotes EGFR phosphorylation in breast cancer cells (Fig. 3G ...phosphorylation (Figure 2E). Since protein phosphorylation sometimes results in a mobility shift in SDS-PAGE, we used a phospho-tag to capture phospho

  6. Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development.

    PubMed

    Bonilla-Claudio, Margarita; Wang, Jun; Bai, Yan; Klysik, Elzbieta; Selever, Jennifer; Martin, James F

    2012-02-01

    We performed an in depth analysis of Bmp4, a critical regulator of development, disease, and evolution, in cranial neural crest (CNC). Conditional Bmp4 overexpression, using a tetracycline-regulated Bmp4 gain-of-function allele, resulted in facial skeletal changes that were most dramatic after an E10.5 Bmp4 induction. Expression profiling uncovered a signature of Bmp4-induced genes (BIG) composed predominantly of transcriptional regulators that control self-renewal, osteoblast differentiation and negative Bmp autoregulation. The complimentary experiment, CNC inactivation of Bmp2, Bmp4 and Bmp7, resulted in complete or partial loss of multiple CNC-derived skeletal elements, revealing a crucial requirement for Bmp signaling in membranous bone and cartilage development. Importantly, the BIG signature was reduced in Bmp loss-of-function mutants, indicating Bmp-regulated target genes are modulated by Bmp dose. Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation. These data support the hypothesis that Bmp signaling regulates craniofacial skeletal development by balancing self-renewal and differentiation pathways in CNC progenitors.

  7. Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

    PubMed

    Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

    2016-10-24

    The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor.

    PubMed

    Zheng, X; Goodwin, A F; Tian, H; Jheon, A H; Klein, O D

    2017-11-01

    The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration. Utilizing models of Ras dysregulation as well as inhibitors of the MAPK and PI3K pathways, we found that MAPK and PI3K regulate dental epithelial stem cell activity, transit-amplifying cell proliferation, and enamel formation in the mouse incisor.

  9. Regulation of TNF-Related Apoptosis-Inducing Ligand Signaling by Glycosylation

    PubMed Central

    2018-01-01

    Tumor necrosis-factor related apoptosis-inducing ligand, also known as TRAIL or APO2L (Apo-2 ligand), is a cytokine of the TNF superfamily acknowledged for its ability to trigger selective apoptosis in tumor cells while being relatively safe towards normal cells. Its binding to its cognate agonist receptors, namely death receptor 4 (DR4) and/or DR5, can induce the formation of a membrane-bound macromolecular complex, coined DISC (death-signaling inducing complex), necessary and sufficient to engage the apoptotic machinery. At the very proximal level, TRAIL DISC formation and activation of apoptosis is regulated both by antagonist receptors and by glycosylation. Remarkably, though, despite the fact that all membrane-bound TRAIL receptors harbor putative glycosylation sites, only pro-apoptotic signaling through DR4 and DR5 has, so far, been found to be regulated by N- and O-glycosylation, respectively. Because putative N-glycosylation sequons and O-glycosylation sites are also found and conserved in all these receptors throughout all animal species (in which these receptors have been identified), glycosylation is likely to play a more prominent role than anticipated in regulating receptor/receptor interactions or trafficking, ultimately defining cell fate through TRAIL stimulation. This review aims to present and discuss these emerging concepts, the comprehension of which is likely to lead to innovative anticancer therapies. PMID:29498673

  10. N-acetylcysteine negatively regulates Notch3 and its malignant signaling

    PubMed Central

    Zhu, Juan-Juan; Liu, Xue-Xia; You, Hui; Gong, Mei-Ying; Zou, Ming; Cheng, Wen-Hsing; Zhu, Jian-Hong

    2016-01-01

    Notch3 receptor is expressed in a variety of cancers and the excised active intracellular domain (N3ICD) initiates its signaling cascade. N-acetylcysteine (NAC) as an antioxidant has been implicated in cancer prevention and therapy. In this study, we demonstrated a negative regulation of Notch3 by NAC in cancer cells. HeLa cells treated with NAC exhibited a time- and concentration-dependent decrease in Notch3 levels and its downstream effectors Hes1 and HRT1 in a manner independent of f-secretase or glutathione. In contrast, NAC did not affect protein levels of Notch1, the full length Notch3 precursor, or ectopically expressed N3ICD. Although SOD, catalase and NAC suppressed reactive oxygen species in HeLa cells, the first two antioxidants did not impact on Notch3 levels. While the mRNA expression of Notch3 was not altered by NAC, functional inhibition of lysosome, but not proteasome, blocked the NAC-dependent reduction of Notch3 levels. Furthermore, results from Notch3 silencing and N3ICD overexpression demonstrated that NAC prevented malignant phenotypes through down-regulation of Notch3 protein in multiple cancer cells. In summary, NAC reduces Notch3 levels through lysosome-dependent protein degradation, thereby negatively regulates Notch3 malignant signaling in cancer cells. These results implicate a novel NAC treatment in sensitizing Notch3-expressing tumors. PMID:27102435

  11. N-acetylcysteine negatively regulates Notch3 and its malignant signaling.

    PubMed

    Zhang, Xiong; Wang, Ya-Nan; Zhu, Juan-Juan; Liu, Xue-Xia; You, Hui; Gong, Mei-Ying; Zou, Ming; Cheng, Wen-Hsing; Zhu, Jian-Hong

    2016-05-24

    Notch3 receptor is expressed in a variety of cancers and the excised active intracellular domain (N3ICD) initiates its signaling cascade. N-acetylcysteine (NAC) as an antioxidant has been implicated in cancer prevention and therapy. In this study, we demonstrated a negative regulation of Notch3 by NAC in cancer cells. HeLa cells treated with NAC exhibited a time- and concentration-dependent decrease in Notch3 levels and its downstream effectors Hes1 and HRT1 in a manner independent of f-secretase or glutathione. In contrast, NAC did not affect protein levels of Notch1, the full length Notch3 precursor, or ectopically expressed N3ICD. Although SOD, catalase and NAC suppressed reactive oxygen species in HeLa cells, the first two antioxidants did not impact on Notch3 levels. While the mRNA expression of Notch3 was not altered by NAC, functional inhibition of lysosome, but not proteasome, blocked the NAC-dependent reduction of Notch3 levels. Furthermore, results from Notch3 silencing and N3ICD overexpression demonstrated that NAC prevented malignant phenotypes through down-regulation of Notch3 protein in multiple cancer cells. In summary, NAC reduces Notch3 levels through lysosome-dependent protein degradation, thereby negatively regulates Notch3 malignant signaling in cancer cells. These results implicate a novel NAC treatment in sensitizing Notch3-expressing tumors.

  12. Acetylation-Dependent Regulation of Notch Signaling in Macrophages by SIRT1 Affects Sepsis Development

    PubMed Central

    Bai, Xiaozhi; He, Ting; Liu, Yang; Zhang, Julei; Li, Xiaoqiang; Shi, Jihong; Wang, Kejia; Han, Fu; Zhang, Wei; Zhang, Yijie; Cai, Weixia; Hu, Dahai

    2018-01-01

    SIRT1 is reported to participate in macrophage differentiation and affect sepsis, and Notch signaling is widely reported to influence inflammation and macrophage activation. However, the specific mechanisms through which SIRT1 regulates sepsis and the relationship between SIRT1 and Notch signaling remain poorly elucidated. In this study, we found that SIRT1 levels were decreased in sepsis both in vitro and in vivo and that SIRT1 regulation of Notch signaling affected inflammation. In lipopolysaccharide (LPS)-induced sepsis, the levels of Notch signaling molecules, including Notch1, Notch2, Hes1, and intracellular domain of Notch (NICD), were increased. However, NICD could be deacetylated by SIRT1, and this led to the suppression of Notch signaling. Notably, in macrophages from myeloid-specific RBP-J−/− mice, in which Notch signaling is inhibited, pro-inflammatory cytokines were expressed at lower levels than in macrophages from wild-type littermates and in RBP-J−/− macrophages, and the NF-κB pathway was also inhibited. Accordingly, in the case of RBP-J−/− mice, LPS-induced inflammation and mortality were lower than in wild-type mice. Our results indicate that SIRT1 inhibits Notch signaling through NICD deacetylation and thus ultimately alleviates sepsis. PMID:29867921

  13. A MicroRNA-Mediated Insulin Signaling Pathway Regulates the Toxicity of Multi-Walled Carbon Nanotubes in Nematode Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Zhao, Yunli; Yang, Junnian; Wang, Dayong

    2016-03-01

    The underlying mechanisms for functions of microRNAs (miRNAs) in regulating toxicity of nanomaterials are largely unclear. Using Illumina HiSeqTM 2000 sequencing technique, we obtained the dysregulated mRNA profiling in multi-walled carbon nanotubes (MWCNTs) exposed nematodes. Some dysregulated genes encode insulin signaling pathway. Genetic experiments confirmed the functions of these dysregulated genes in regulating MWCNTs toxicity. In the insulin signaling pathway, DAF-2/insulin receptor regulated MWCNTs toxicity by suppressing function of DAF-16/FOXO transcription factor. Moreover, we raised a miRNAs-mRNAs network involved in the control of MWCNTs toxicity. In this network, mir-355 might regulate MWCNTs toxicity by inhibiting functions of its targeted gene of daf-2, suggesting that mir-355 may regulate functions of the entire insulin signaling pathway by acting as an upregulator of DAF-2, the initiator of insulin signaling pathway, in MWCNTs exposed nematodes. Our results provides highlight on understanding the crucial role of miRNAs in regulating toxicity of nanomaterials in organisms.

  14. SPSB1, a Novel Negative Regulator of the Transforming Growth Factor-β Signaling Pathway Targeting the Type II Receptor.

    PubMed

    Liu, Sheng; Nheu, Thao; Luwor, Rodney; Nicholson, Sandra E; Zhu, Hong-Jian

    2015-07-17

    Appropriate cellular signaling is essential to control cell proliferation, differentiation, and cell death. Aberrant signaling can have devastating consequences and lead to disease states, including cancer. The transforming growth factor-β (TGF-β) signaling pathway is a prominent signaling pathway that has been tightly regulated in normal cells, whereas its deregulation strongly correlates with the progression of human cancers. The regulation of the TGF-β signaling pathway involves a variety of physiological regulators. Many of these molecules act to alter the activity of Smad proteins. In contrast, the number of molecules known to affect the TGF-β signaling pathway at the receptor level is relatively low, and there are no known direct modulators for the TGF-β type II receptor (TβRII). Here we identify SPSB1 (a Spry domain-containing Socs box protein) as a novel regulator of the TGF-β signaling pathway. SPSB1 negatively regulates the TGF-β signaling pathway through its interaction with both endogenous and overexpressed TβRII (and not TβRI) via its Spry domain. As such, TβRII and SPSB1 co-localize on the cell membrane. SPSB1 maintains TβRII at a low level by enhancing the ubiquitination levels and degradation rates of TβRII through its Socs box. More importantly, silencing SPSB1 by siRNA results in enhanced TGF-β signaling and migration and invasion of tumor cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Somatostatin signaling and the regulation of growth and metabolism in fish.

    PubMed

    Klein, Sarah E; Sheridan, Mark A

    2008-05-14

    The study of the somatostatins (SS) signaling system in fish has provided important information about the structure, function, and evolution of SSs and their receptors. The SS signaling system elicits widespread biological actions via multiple hormone variants, numerous receptor subtypes, and a variety of signal transduction pathways. SSs alter growth via both direct and indirect actions, including inhibiting growth hormone release at the pituitary, decreasing hepatic GH sensitivity, and lowering plasma IGF-I levels. Metabolism also is significantly influenced by SSs. SSs stimulate the breakdown of energy stores and influences digestion, food intake, nutrient absorption, and food conversion both directly and through the modulation of other hormonal systems. The study of fish, which display a diversity of habitat types and life history forms, reveals that the SS signaling system helps regulate energy partitioning and integrate metabolism with growth and other biological processes.

  16. RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling.

    PubMed

    Zhang, Min; Zhang, Ping; Liu, Yunsong; Lv, Longwei; Zhang, Xiao; Liu, Hao; Zhou, Yongsheng

    2017-02-21

    The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling. Further, silencing of LGR4 inhibited the activity of ERK signalling and osteogenic differentiation of hASCs. Most importantly, we found that loss of LGR4 abrogated RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signalling inhibition. Collectively, our data show that ERK signalling works downstream of LGR4 and RSPO3 regulates osteoblastic differentiation of hASCs possibly via the LGR4-ERK signalling.

  17. RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling

    PubMed Central

    Zhang, Min; Zhang, Ping; Liu, Yunsong; Lv, Longwei; Zhang, Xiao; Liu, Hao; Zhou, Yongsheng

    2017-01-01

    The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling. Further, silencing of LGR4 inhibited the activity of ERK signalling and osteogenic differentiation of hASCs. Most importantly, we found that loss of LGR4 abrogated RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signalling inhibition. Collectively, our data show that ERK signalling works downstream of LGR4 and RSPO3 regulates osteoblastic differentiation of hASCs possibly via the LGR4-ERK signalling. PMID:28220828

  18. Myostatin: a novel insight into its role in metabolism, signal pathways, and expression regulation.

    PubMed

    Huang, Zhiqing; Chen, Xiaoling; Chen, Daiwen

    2011-09-01

    Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a critical autocrine/paracrine inhibitor of skeletal muscle growth. Since the first observed double-muscling phenotype was reported in myostatin-null animals, a functional role of myostatin has been demonstrated in the control of skeletal muscle development. However, beyond the confines of its traditional role in muscle growth inhibition, myostatin has recently been shown to play an important role in metabolism. During the past several years, it has been well established that Smads are canonical mediators of signals for myostatin from the receptors to the nucleus. However, growing evidence supports the notion that Non-Smad signal pathways also participate in myostatin signaling. Myostatin expression is increased in muscle atrophy and metabolic disorders, suggesting that changes in endogenous expression of myostatin may provide therapeutic benefit for these diseases. MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate gene expression and recent evidence has accumulated supporting a role for miRNAs in the regulation of myostatin expression. This review highlights some of these areas in myostatin research: a novel role in metabolism, signal pathways, and miRNA-mediated expression regulation. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Mitochondrial Ion Channels/Transporters as Sensors and Regulators of Cellular Redox Signaling

    PubMed Central

    Ryu, Shin-Young; Jhun, Bong Sook; Hurst, Stephen

    2014-01-01

    Abstract Significance: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently. Recent Advances: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, mitochondrial permeability transition pore, and mitochondrial ATP-sensitive K+ channel. This new information enables us to form detailed molecular and functional characterizations of mitochondrial ion channels/transporters and their roles in mitochondrial redox signaling. Critical Issues: Redox-mediated post-translational modifications of mitochondrial ion channels/transporters and ETC serve as key mechanisms for the spatiotemporal control of mitochondrial ROS/RNS generation. Future Directions: Identification of detailed molecular mechanisms for redox-mediated regulation of mitochondrial ion channels will enable us to find novel therapeutic targets for many diseases that are associated with cellular redox signaling and mitochondrial ion channels/transporters. Antioxid. Redox Signal. 21, 987–1006. PMID:24180309

  20. A Phenotype-Based RNAi Screening for Ras-ERK/MAPK Signaling-Associated Stem Cell Regulators in C. elegans.

    PubMed

    Lee, Myon-Hee; Yoon, Dong Suk

    2017-01-01

    Stem cells have the ability to self-renew and to generate differentiated cell types. A regulatory network that controls this balance is critical for stem cell homeostasis and normal animal development. Particularly, Ras-ERK/MAPK signaling pathway is critical for stem cell self-renewal and differentiation in mammals, including humans. Aberrant regulation of Ras-ERK/MAPK signaling pathway results in either stem cell or overproliferation. Therefore, the identification of Ras-ERK/MAPK signaling pathway-associated regulators is critical to understand the mechanism of stem cell (possibly cancer stem cell) control. In this report, using the nematode C. elegans mutants, we developed a methodology for a phenotype-based RNAi screening that identifies stem cell regulator genes associated with Ras-ERK/MAPK signaling within the context of a whole organism. Importantly, this phenotype-based RNAi screening can be applied for other stem cell-associated signaling pathways such as Wnt/β-catenin and Notch using the C. elegans.