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Sample records for cell polarization processes

  1. Cell polarity

    PubMed Central

    Romereim, Sarah M

    2011-01-01

    Despite extensive genetic analysis of the dynamic multi-phase process that transforms a small population of lateral plate mesoderm into the mature limb skeleton, the mechanisms by which signaling pathways regulate cellular behaviors to generate morphogenetic forces are not known. Recently, a series of papers have offered the intriguing possibility that regulated cell polarity fine-tunes the morphogenetic process via orienting cell axes, division planes and cell movements. Wnt5a-mediated non-canonical signaling, which may include planar cell polarity, has emerged as a common thread in the otherwise distinct signaling networks that regulate morphogenesis in each phase of limb development. These findings position the limb as a key model to elucidate how global tissue patterning pathways direct local differences in cell behavior that, in turn, generate growth and form. PMID:22064549

  2. Polarized cells, polar actions.

    PubMed

    Maddock, J R; Alley, M R; Shapiro, L

    1993-11-01

    The recognition of polar bacterial organization is just emerging. The examples of polar localization given here are from a variety of bacterial species and concern a disparate array of cellular functions. A number of well-characterized instances of polar localization of bacterial proteins, including the chemoreceptor complex in both C. crescentus and E. coli, the maltose-binding protein in E. coli, the B. japonicum surface attachment proteins, and the actin tail of L. monocytogenes within a mammalian cell, involve proteins or protein complexes that facilitate bacterial interaction with the environment, either the extracellular milieux or that within a plant or mammalian host. The significance of this observation remains unclear. Polarity in bacteria poses many problems, including the necessity for a mechanism for asymmetrically distributing proteins as well as a mechanism by which polar localization is maintained. Large structures, such as a flagellum, are anchored at the pole by means of the basal body that traverses the peptidoglycan wall. But for proteins and small complexes, whether in the periplasm or the membrane, one must invoke a mechanism that prevents the diffusion of these proteins away from the cell pole. Perhaps the periplasmic proteins are retained at the pole by the presence of the periseptal annulus (35). The constraining features for membrane components are not known. For large aggregates, such as the clusters of MCP, CheA, and CheW complexes, perhaps the size of the aggregate alone prevents displacement. In most cases of cellular asymmetry, bacteria are able to discriminate between the new pole and the old pole and to utilize this information for localization specificity. The maturation of new pole to old pole appears to be a common theme as well. Given numerous examples reported thus far, we propose that bacterial polarity displays specific rules and is a more general phenomenon than has been previously recognized.

  3. How B cells capture, process and present antigens: a crucial role for cell polarity.

    PubMed

    Yuseff, Maria-Isabel; Pierobon, Paolo; Reversat, Anne; Lennon-Duménil, Ana-Maria

    2013-07-01

    B cells are key components of the adaptive immune response. Their differentiation into either specific memory B cells or antibody-secreting plasma cells is a consequence of activation steps that involve the processing and presentation of antigens. The engagement of B cell receptors by surface-tethered antigens leads to the formation of an immunological synapse that coordinates cell signalling events and that promotes antigen uptake for presentation on MHC class II molecules. In this Review, we discuss membrane trafficking and the associated molecular mechanisms that are involved in antigen extraction and processing at the B cell synapse, and we highlight how B cells use cell polarity to coordinate the complex events that ultimately lead to efficient humoral responses.

  4. Cell polarization, a crucial process in fungal defence.

    PubMed

    Schmelzer, Elmon

    2002-09-01

    Plant cells responding to fungal attack undergo large morphological alterations, along with rapid and extensive metabolic reprogramming. Cytological analysis of single infected plant cells revealed a large complexity of interdependent, rapid and dynamic changes of a multitude of cellular components. Among these changes are major rearrangements of the cytoskeleton, translocation of cytoplasm and of the cell nucleus to the fungal penetration site, and local apposition of barrier material around this site, which results in massive cell-wall reinforcement. If this first line of defence is overcome by the pathogen, in many cases, it is followed by hypersensitive plant cell death, which stops growth of the penetrating fungus and finally leads to its death. The speed and magnitude of the initial defence response appear to be crucial to plant disease resistance.

  5. Cell polarity: mechanochemical patterning.

    PubMed

    Goehring, Nathan W; Grill, Stephan W

    2013-02-01

    Nearly every cell type exhibits some form of polarity, yet the molecular mechanisms vary widely. Here we examine what we term 'chemical systems' where cell polarization arises through biochemical interactions in signaling pathways, 'mechanical systems' where cells polarize due to forces, stresses and transport, and 'mechanochemical systems' where polarization results from interplay between mechanics and chemical signaling. To reveal potentially unifying principles, we discuss mathematical conceptualizations of several prototypical examples. We suggest that the concept of local activation and global inhibition - originally developed to explain spatial patterning in reaction-diffusion systems - provides a framework for understanding many cases of cell polarity. Importantly, we find that the core ingredients in this framework - symmetry breaking, self-amplifying feedback, and long-range inhibition - involve processes that can be chemical, mechanical, or even mechanochemical in nature.

  6. Polarization Radar Processing Technology

    DTIC Science & Technology

    1989-10-01

    Oi"C FILE ( J qII RADC-TR-89-144 In-House Report October 1989 AD-A215 242 POLARIZATION RADAR PROCESSING TECHNOLOGY Kenneth C. Stiefvater, Russell D...NO. NO. NO. ACCESSION NO. 62702F 4506 11 58 11. TITLE (Include Security Classification) POLARIZATION RADAR PROCESSING TECHNOLOGY 12. PERSONAL AUTHOR(S

  7. B Cells use Conserved Polarity Cues to Regulate Their Antigen Processing and Presentation Functions

    PubMed Central

    Yuseff, Maria-Isabel; Lennon-Duménil, Ana Maria

    2015-01-01

    The ability of B cells to produce high-affinity antibodies and to establish immunological memory in response to a wide range of pathogenic antigens is an essential part of the adaptive immune response. The initial step that triggers a humoral immune response involves the acquisition of antigens by B cells via their surface immunoglobulin, the B cell receptor (BCR). BCR-engaged antigens are transported into specialized lysosomal compartments where proteolysis and production of MHC class II-peptide complexes occur, a process referred to as antigen processing. Expression of MHC class II complexes at the B cell surface allows them to interact with T cells and to receive their help to become fully activated. In this review, we describe how B cells rely on conserved cell polarity mechanisms to coordinate local proteolytic secretion and mechanical forces at the B cell synapse enabling them to efficiently acquire and present extracellular antigens. We foresee that the mechanisms that dictate B cell activation can be used to tune B cell responses in the context of autoimmune diseases and cancer. PMID:26074919

  8. Axonal Degeneration in Retinal Ganglion Cells Is Associated with a Membrane Polarity-Sensitive Redox Process

    PubMed Central

    Catrinescu, Maria-Magdalena; Binan, Loïc; Costantino, Santiago

    2017-01-01

    Axonal degeneration is a pathophysiological mechanism common to several neurodegenerative diseases. The slow Wallerian degeneration (WldS) mutation, which results in reduced axonal degeneration in the central and peripheral nervous systems, has provided insight into a redox-dependent mechanism by which axons undergo self-destruction. We studied early molecular events in axonal degeneration with single-axon laser axotomy and time-lapse imaging, monitoring the initial changes in transected axons of purified retinal ganglion cells (RGCs) from wild-type and WldS rat retinas using a polarity-sensitive annexin-based biosensor (annexin B12-Cys101,Cys260-N,N′-dimethyl-N-(iodoacetyl)-N′-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) ethylenediamine). Transected axons demonstrated a rapid and progressive change in membrane phospholipid polarity, manifested as phosphatidylserine externalization, which was significantly delayed and propagated more slowly in axotomized WldS RGCs compared with wild-type axons. Delivery of bis(3-propionic acid methyl ester)phenylphosphine borane complex, a cell-permeable intracellular disulfide-reducing drug, slowed the onset and velocity of phosphatidylserine externalization in wild-type axons significantly, replicating the WldS phenotype, whereas extracellular redox modulation reversed the WldS phenotype. These findings are consistent with an intra-axonal redox mechanism for axonal degeneration associated with the initiation and propagation of phosphatidylserine externalization after axotomy. SIGNIFICANCE STATEMENT Axonal degeneration is a neuronal process independent of somal apoptosis, the propagation of which is unclear. We combined single-cell laser axotomy with time-lapse imaging to study the dynamics of phosphatidylserine externalization immediately after axonal injury in purified retinal ganglion cells. The extension of phosphatidylserine externalization was slowed and delayed in Wallerian degeneration slow (WldS) axons and this phenotype could

  9. Normalized Polarization Ratios for the Analysis of Cell Polarity

    PubMed Central

    Shimoni, Raz; Pham, Kim; Yassin, Mohammed; Ludford-Menting, Mandy J.; Gu, Min; Russell, Sarah M.

    2014-01-01

    The quantification and analysis of molecular localization in living cells is increasingly important for elucidating biological pathways, and new methods are rapidly emerging. The quantification of cell polarity has generated much interest recently, and ratiometric analysis of fluorescence microscopy images provides one means to quantify cell polarity. However, detection of fluorescence, and the ratiometric measurement, is likely to be sensitive to acquisition settings and image processing parameters. Using imaging of EGFP-expressing cells and computer simulations of variations in fluorescence ratios, we characterized the dependence of ratiometric measurements on processing parameters. This analysis showed that image settings alter polarization measurements; and that clustered localization is more susceptible to artifacts than homogeneous localization. To correct for such inconsistencies, we developed and validated a method for choosing the most appropriate analysis settings, and for incorporating internal controls to ensure fidelity of polarity measurements. This approach is applicable to testing polarity in all cells where the axis of polarity is known. PMID:24963926

  10. Normalized polarization ratios for the analysis of cell polarity.

    PubMed

    Shimoni, Raz; Pham, Kim; Yassin, Mohammed; Ludford-Menting, Mandy J; Gu, Min; Russell, Sarah M

    2014-01-01

    The quantification and analysis of molecular localization in living cells is increasingly important for elucidating biological pathways, and new methods are rapidly emerging. The quantification of cell polarity has generated much interest recently, and ratiometric analysis of fluorescence microscopy images provides one means to quantify cell polarity. However, detection of fluorescence, and the ratiometric measurement, is likely to be sensitive to acquisition settings and image processing parameters. Using imaging of EGFP-expressing cells and computer simulations of variations in fluorescence ratios, we characterized the dependence of ratiometric measurements on processing parameters. This analysis showed that image settings alter polarization measurements; and that clustered localization is more susceptible to artifacts than homogeneous localization. To correct for such inconsistencies, we developed and validated a method for choosing the most appropriate analysis settings, and for incorporating internal controls to ensure fidelity of polarity measurements. This approach is applicable to testing polarity in all cells where the axis of polarity is known.

  11. Wnt-Dependent Control of Cell Polarity in Cultured Cells.

    PubMed

    Runkle, Kristin B; Witze, Eric S

    2016-01-01

    The secreted ligand Wnt5a regulates cell polarity and polarized cell movement during development by signaling through the poorly defined noncanonical Wnt pathway. Cell polarity regulates most aspects of cell behavior including the organization of apical/basolateral membrane domains of epithelial cells, polarized cell divisions along a directional plane, and front rear polarity during cell migration. These characteristics of cell polarity allow coordinated cell movements required for tissue formation and organogenesis during embryonic development. Genetic model organisms have been used to identify multiple signaling pathways including Wnt5a that are required to establish cell polarity and regulate polarized cell behavior. However, the downstream signaling events that regulate these complex cellular processes are still poorly understood. The methods below describe assays to study Wnt5a-induced cell polarity in cultured cells, which may facilitate our understanding of these complex signaling pathways.

  12. Cell Polarity Signaling in Arabidopsis

    PubMed Central

    Yang, Zhenbiao

    2009-01-01

    Cell polarization is intimately linked to plant development, growth, and responses to the environment. Major advances have been made in our understanding of the signaling pathways and networks that regulate cell polarity in plants owing to recent studies on several model systems, e.g., tip growth in pollen tubes, cell morphogenesis in the leaf epidermis, and polar localization of PINs. From these studies we have learned that plant cells use conserved mechanisms such as Rho family GTPases to integrate both plant-specific and conserved polarity cues and to coordinate the cytoskeketon dynamics/reorganization and vesicular trafficking required for polarity establishment and maintenance. This review focuses upon signaling mechanisms for cell polarity formation in Arabidopsis, with an emphasis on Rho GTPase signaling in polarized cell growth and how these mechanisms compare with those for cell polarity signaling in yeast and animal systems. PMID:18837672

  13. Cell Polarization: A Comparative Cell Biology and Immunological View

    PubMed Central

    Vicente-Manzanares, Miguel

    2000-01-01

    Cell polarization and the establishment of functionally specialized domains play a pivotal role in many cellular processes such as vectorial transport of molecules, cell division and differentiation, directional movement of the cells in a chemotactic gradient and activation of the immune response. Cell polarization is a complex phenomenon, in which the interplay among cell cytoskeletal components, extra- and intracellular signals and organelle and membrane reorganization is crucial to achieve a correct cell shape change. The intracellular machinery needed for cell polarization has been elucidated in several well-established models, including yeast, epithelial, neuronal and germ-line cells. Cells of the immune system also polarize in response to extracellular cues, but many of the intracellular signals that control cell polarization and the role of genes with a well-defined function in other polarization processes are still unknown. In this review, recent advances in the study of leukocyte polarization are examined highlighting the similarities and differences with other models of cell polarization. The extracellular signals which direct cell polarization, the signal transduction pathways involved as well as the role of cell polarization in the development of the immune response are discussed. PMID:11097201

  14. Integrins and epithelial cell polarity.

    PubMed

    Lee, Jessica L; Streuli, Charles H

    2014-08-01

    Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell-matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical-basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity.

  15. Planar cell polarity of the kidney.

    PubMed

    Schnell, Ulrike; Carroll, Thomas J

    2016-05-01

    Planar cell polarity (PCP) or tissue polarity refers to the polarization of tissues perpendicular to the apical-basal axis. Most epithelia, including the vertebrate kidney, show signs of planar polarity. In the kidney, defects in planar polarity are attributed to several disease states including multiple forms of cystic kidney disease. Indeed, planar cell polarity has been shown to be essential for several cellular processes that appear to be necessary for establishing and maintaining tubule diameter. However, uncovering the genetic mechanisms underlying PCP in the kidney has been complicated as the roles of many of the main players are not conserved in flies and vice versa. Here, we review a number of cellular and molecular processes that can affect PCP of the kidney with a particular emphasis on the mechanisms that do not appear to be conserved in flies or that are not part of canonical determinants.

  16. Novel and Robust Transplantation Reveals the Acquisition of Polarized Processes by Cortical Cells Derived from Mouse and Human Pluripotent Stem Cells

    PubMed Central

    Nagashima, Fumiaki; Suzuki, Ikuo K.; Shitamukai, Atsunori; Sakaguchi, Haruko; Iwashita, Misato; Kobayashi, Taeko; Tone, Shigenobu; Toida, Kazunori; Vanderhaeghen, Pierre

    2014-01-01

    Current stem cell technologies have enabled the induction of cortical progenitors and neurons from embryonic stem cells (ESCs) and induced pluripotent stem cells in vitro. To understand the mechanisms underlying the acquisition of apico-basal polarity and the formation of processes associated with the stemness of cortical cells generated in monolayer culture, here, we developed a novel in utero transplantation system based on the moderate dissociation of adherens junctions in neuroepithelial tissue. This method enables (1) the incorporation of remarkably higher numbers of grafted cells and (2) quantitative morphological analyses at single-cell resolution, including time-lapse recording analyses. We then grafted cortical progenitors induced from mouse ESCs into the developing brain. Importantly, we revealed that the mode of process extension depends on the extrinsic apico-basal polarity of the host epithelial tissue, as well as on the intrinsic differentiation state of the grafted cells. Further, we successfully transplanted cortical progenitors induced from human ESCs, showing that our strategy enables investigation of the neurogenesis of human neural progenitors within the developing mouse cortex. Specifically, human cortical cells exhibit multiple features of radial migration. The robust transplantation method established here could be utilized both to uncover the missing gap between neurogenesis from ESCs and the tissue environment and as an in vivo model of normal and pathological human corticogenesis. PMID:24325299

  17. The Drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development.

    PubMed

    Djiane, Alexandre; Mlodzik, Marek

    2010-06-21

    Epithelia often show, in addition to the ubiquitous apico-basal (A/B) axis, a polarization within the plane of the epithelium, perpendicular to the A/B axis. Such planar cell polarity (PCP) is for example evident in the regular arrangement of the stereocilia in the cochlea of the mammalian inner ear or in (almost) all Drosophila adult external structures. GIPCs (GAIP interacting protein, C terminus) were first identified in mammals and bind to the Galphai GTPase activating protein RGS-GAIP. They have been proposed to act in a G-protein coupled complex controlling vesicular trafficking. Although GIPCs have been found to bind to numerous proteins including Frizzled receptors, which participate in PCP establishment, there is little in vivo evidence for the functional role(s) of GIPCs. We show here that overexpressed Drosophila dGIPC alters PCP generation in the wing. We were however unable to find any binding between dGIPC and the Drosophila receptors Fz1 and Fz2. The effect of overexpressed dGIPC is likely due to an effect on the actin cytoskeleton via myosins, since it is almost entirely suppressed by removing a genomic copy of the Myosin VI/jaguar gene. Surprisingly, although dGIPC can interfere with PCP generation and myosin based processes, the complete loss-of-function of dGIPC gives viable adults with no PCP or other detectable defects arguing for a non-essential role of dGIPC in viability and normal Drosophila development.

  18. Polarized cells, polarized views: asymmetric cell division in hematopoietic cells.

    PubMed

    Pham, Kim; Sacirbegovic, Faruk; Russell, Sarah M

    2014-01-01

    It has long been recognized that alterations in cell shape and polarity play important roles in coordinating lymphocyte functions. In the last decade, a new aspect of lymphocyte polarity has attracted much attention, termed asymmetric cell division (ACD). ACD has previously been shown to dictate or influence many aspects of development in model organisms such as the worm and the fly, and to be disrupted in disease. Recent observations that ACD also occurs in lymphocytes led to exciting speculations that ACD might influence lymphocyte differentiation and function, and leukemia. Dissecting the role that ACD might play in these activities has not been straightforward, and the evidence to date for a functional role in lymphocyte fate determination has been controversial. In this review, we discuss the evidence to date for ACD in lymphocytes, and how it might influence lymphocyte fate. We also discuss current gaps in our knowledge, and suggest approaches to definitively test the physiological role of ACD in lymphocytes.

  19. Polarized Cells, Polarized Views: Asymmetric Cell Division in Hematopoietic Cells

    PubMed Central

    Pham, Kim; Sacirbegovic, Faruk; Russell, Sarah M.

    2014-01-01

    It has long been recognized that alterations in cell shape and polarity play important roles in coordinating lymphocyte functions. In the last decade, a new aspect of lymphocyte polarity has attracted much attention, termed asymmetric cell division (ACD). ACD has previously been shown to dictate or influence many aspects of development in model organisms such as the worm and the fly, and to be disrupted in disease. Recent observations that ACD also occurs in lymphocytes led to exciting speculations that ACD might influence lymphocyte differentiation and function, and leukemia. Dissecting the role that ACD might play in these activities has not been straightforward, and the evidence to date for a functional role in lymphocyte fate determination has been controversial. In this review, we discuss the evidence to date for ACD in lymphocytes, and how it might influence lymphocyte fate. We also discuss current gaps in our knowledge, and suggest approaches to definitively test the physiological role of ACD in lymphocytes. PMID:24550912

  20. Cell Polarity Proteins in Breast Cancer Progression.

    PubMed

    Rejon, Carlis; Al-Masri, Maia; McCaffrey, Luke

    2016-10-01

    Breast cancer, one of the leading causes of cancer related death in women worldwide, is a heterogeneous disease with diverse subtypes that have different properties and prognoses. The developing mammary gland is a highly proliferative and invasive tissue, and some of the developmental programs may be aberrantly activated to promote breast cancer progression. In the breast, luminal epithelial cells exhibit apical-basal polarity, and the failure to maintain this organizational structure, due to disruption of polarity complexes, is implicated in promoting hyperplasia and tumors. Therefore, understanding the mechanisms underlying loss of polarity will contribute to our knowledge of the early stages leading to the pathogenesis of the disease. In this review, we will discuss recent findings that support the idea that loss of apical-basal cell polarity is a crucial step in the acquisition of the malignant phenotype. Oncogene induced loss of tissue organization shares a conserved cellular mechanism with developmental process, we will further describe the role of the individual polarity complexes, the Par, Crumbs, and Scribble, to couple cell division orientation and cell growth. We will examine symmetric or asymmetric cell divisions in mammary stem cell and their contribution to the development of breast cancer subtypes and cancer stem cells. Finally, we will highlight some of the recent advances in our understanding of the molecular mechanisms by which changes in epithelial polarity programs promote invasion and metastasis through single cell and collective cell modes. J. Cell. Biochem. 117: 2215-2223, 2016. © 2016 Wiley Periodicals, Inc.

  1. Profiling Signaling Polarity in Chemotactic Cells

    SciTech Connect

    Wang, Yingchun; Ding, Shi-Jian; Wang, Wei; Jacobs, Jon M.; Qian, Weijun; Moore, Ronald J.; Yang, Feng; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2007-05-15

    While directional movement requires morphological polarization characterized by formation of a leading pseudopodium at the front and a trailing rear at the back, little is known about how protein networks are spatially integrated to regulate this process. Here, we utilize a unique pseudopodial purification system and quantitative proteomics and phosphoproteomics to map the spatial relationship of 3509 proteins and 228 distinct sites of phosphorylation in polarized cells. Networks of signaling proteins, metabolic pathways, actin regulatory proteins, and kinase-substrate cascades were found to partition to different poles of the cell including components of the Ras/ERK pathway. Also, several novel proteins were found to be differentially phosphorylated at the front or rear of polarized cells and to localize to distinct subcellular structures. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive profile of proteins and their sites of phosphorylation that control cell polarization.

  2. Integrins and epithelial cell polarity

    PubMed Central

    Lee, Jessica L.; Streuli, Charles H.

    2014-01-01

    ABSTRACT Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell–matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical–basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity. For further reading, please see related articles: ‘ERM proteins at a glance’ by Andrea McClatchey (J. Cell Sci. 127, 3199–3204). ‘Establishment of epithelial polarity – GEF who's minding the GAP?’ by Siu Ngok et al. (J. Cell Sci. 127, 3205–3215). PMID:24994933

  3. Tissue Morphodynamics: Translating Planar Polarity Cues into Polarized Cell Behaviors

    PubMed Central

    Devenport, Danelle

    2016-01-01

    The ability of cells to collectively orient and align their behaviors is essential in multicellular organisms for unidirectional cilia beating, collective cell movements, oriented cell divisions, and asymmetric cell fate specification. The planar cell polarity pathway coordinates a vast and diverse array of collective cell behaviors by intersecting with downstream pathways that regulate cytoskeletal dynamics and intercellular signaling. How the planar polarity pathway translates directional cues to produce polarized cell behaviors is the focus of this review. PMID:26994528

  4. Tissue morphodynamics: Translating planar polarity cues into polarized cell behaviors.

    PubMed

    Devenport, Danelle

    2016-07-01

    The ability of cells to collectively orient and align their behaviors is essential in multicellular organisms for unidirectional cilia beating, collective cell movements, oriented cell divisions, and asymmetric cell fate specification. The planar cell polarity pathway coordinates a vast and diverse array of collective cell behaviors by intersecting with downstream pathways that regulate cytoskeletal dynamics and intercellular signaling. How the planar polarity pathway translates directional cues to produce polarized cell behaviors is the focus of this review.

  5. Cell polarity proteins and spermatogenesis.

    PubMed

    Gao, Ying; Xiao, Xiang; Lui, Wing-Yee; Lee, Will M; Mruk, Dolores; Cheng, C Yan

    2016-11-01

    When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells. For instance, Sertoli cell nuclei are found near the basement membrane. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in

  6. Cell Polarity As A Regulator of Cancer Cell Behavior Plasticity

    PubMed Central

    Muthuswamy, Senthil K; Xue, Bin

    2013-01-01

    Cell polarization is an evolutionarily conserved process that facilitates asymmetric distribution of organelles and proteins, is an evolutionarily conserved property that is modified dynamically during physiological processes such as cell division, migration, and morphogenesis. The plasticity with which cells change their behavior and phenotype in response to cell intrinsic and extrinsic cues is an essential feature of normal physiology. In disease states such as cancer, cells lose their ability to behave normally in response to physiological cues. A molecular understanding of mechanisms that alter the behavior of cancer cells is limited. Cell polarity proteins are an recognized class of molecules that can receive and interpret both intrinsic and extrinsic signals to modulate cell behavior. In this review, we discuss how cell polarity proteins regulate a diverse array of biological processes and how they can contribute to alterations in the behavior of cancer cells. PMID:22881459

  7. Polarized Cell Division of Chlamydia trachomatis

    PubMed Central

    Abdelrahman, Yasser; Ouellette, Scot P.; Belland, Robert J.; Cox, John V.

    2016-01-01

    Bacterial cell division predominantly occurs by a highly conserved process, termed binary fission, that requires the bacterial homologue of tubulin, FtsZ. Other mechanisms of bacterial cell division that are independent of FtsZ are rare. Although the obligate intracellular human pathogen Chlamydia trachomatis, the leading bacterial cause of sexually transmitted infections and trachoma, lacks FtsZ, it has been assumed to divide by binary fission. We show here that Chlamydia divides by a polarized cell division process similar to the budding process of a subset of the Planctomycetes that also lack FtsZ. Prior to cell division, the major outer-membrane protein of Chlamydia is restricted to one pole of the cell, and the nascent daughter cell emerges from this pole by an asymmetric expansion of the membrane. Components of the chlamydial cell division machinery accumulate at the site of polar growth prior to the initiation of asymmetric membrane expansion and inhibitors that disrupt the polarity of C. trachomatis prevent cell division. The polarized cell division of C. trachomatis is the result of the unipolar growth and FtsZ-independent fission of this coccoid organism. This mechanism of cell division has not been documented in other human bacterial pathogens suggesting the potential for developing Chlamydia-specific therapeutic treatments. PMID:27505160

  8. Polarized Cell Division of Chlamydia trachomatis.

    PubMed

    Abdelrahman, Yasser; Ouellette, Scot P; Belland, Robert J; Cox, John V

    2016-08-01

    Bacterial cell division predominantly occurs by a highly conserved process, termed binary fission, that requires the bacterial homologue of tubulin, FtsZ. Other mechanisms of bacterial cell division that are independent of FtsZ are rare. Although the obligate intracellular human pathogen Chlamydia trachomatis, the leading bacterial cause of sexually transmitted infections and trachoma, lacks FtsZ, it has been assumed to divide by binary fission. We show here that Chlamydia divides by a polarized cell division process similar to the budding process of a subset of the Planctomycetes that also lack FtsZ. Prior to cell division, the major outer-membrane protein of Chlamydia is restricted to one pole of the cell, and the nascent daughter cell emerges from this pole by an asymmetric expansion of the membrane. Components of the chlamydial cell division machinery accumulate at the site of polar growth prior to the initiation of asymmetric membrane expansion and inhibitors that disrupt the polarity of C. trachomatis prevent cell division. The polarized cell division of C. trachomatis is the result of the unipolar growth and FtsZ-independent fission of this coccoid organism. This mechanism of cell division has not been documented in other human bacterial pathogens suggesting the potential for developing Chlamydia-specific therapeutic treatments.

  9. Signaling Pathways in Cell Polarity

    PubMed Central

    McCaffrey, Luke Martin; Macara, Ian G.

    2012-01-01

    A key function of signal transduction during cell polarization is the creation of spatially segregated regions of the cell cortex that possess different lipid and protein compositions and have distinct functions. Polarity can be initiated spontaneously or in response to signaling inputs from adjacent cells or soluble factors and is stabilized by positive-feedback loops. A conserved group of proteins, the Par proteins, plays a central role in polarity establishment and maintenance in many contexts. These proteins generate and maintain their distinct locations in cells by actively excluding one another from specific regions of the plasma membrane. The Par signaling pathway intersects with multiple other pathways that control cell growth, death, and organization. PMID:22553378

  10. Planar cell polarity in Drosophila

    PubMed Central

    Maung, Saw Myat Thanda W

    2011-01-01

    In all multicellular organisms, epithelial cells are not only polarized along the apical-basal axis, but also within the epithelial plane, giving cells a sense of direction. Planar cell polarity (PCP) signaling regulates establishment of polarity within the plane of an epithelium. The outcomes of PCP signaling are diverse and include the determination of cell fates, the generation of asymmetric but highly aligned structures, such as the stereocilia in the human inner ear or the hairs on a fly wing, or the directional migration of cells during convergence and extension during vertebrate gastrulation. In humans, aberrant PCP signaling can result in severe developmental defects, such as open neural tubes (spina bifida), and can cause cystic kidneys. In this review, we discuss the basic mechanism and more recent findings of PCP signaling focusing on Drosophila melanogaster, the model organism in which most key PCP components were initially identified. PMID:21983142

  11. Cell polarity and planar cell polarity (PCP) in spermatogenesis.

    PubMed

    Chen, Haiqi; Mruk, Dolores D; Lui, Wing-Yee; Wong, Chris K C; Lee, Will M; Cheng, C Yan

    2017-09-28

    In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane and their tails toward the tubule lumen. On the other hand, these polarized spermatids also align across the plane of seminiferous epithelium, mimicking planar cell polarity (PCP) found in other hair cells in cochlea (inner ear). This orderly alignment of developing spermatids during spermiogenesis is important to support spermatogenesis, such that the maximal number of developing spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes. In this review, we provide emerging evidence to demonstrate spermatid PCP in the seminiferous epithelium to support spermatogenesis. We also review findings in the field regarding the biology of spermatid cellular polarity (e.g., head-tail polarity and apico-basal polarity) and its inter-relationship to spermatid PCP. Furthermore, we also provide a hypothetical concept on the importance of PCP proteins in endocytic vesicle-mediated protein trafficking events to support spermatogenesis through protein endocytosis and recycling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Organic photovoltaic cells with controlled polarization sensitivity

    SciTech Connect

    Awartani, Omar; O'Connor, Brendan T.; Kudenov, Michael W.

    2014-03-03

    In this study, we demonstrate linearly polarized organic photovoltaic cells with a well-controlled level of polarization sensitivity. The polarized devices were created through the application of a large uniaxial strain to the bulk heterojunction poly(3-hexylthiophene):Phenyl-C61-butyric acid methyl ester (P3HT:PCBM) film and printing the plastically deformed active layer onto a PEDOT:PSS and indium tin oxide coated glass substrate. The P3HT:PCBM layer is processed such that it is able to accommodate high strains (over 100%) without fracture. After printing the strained films, thermal annealing is used to optimize solar cell performance while maintaining polarization sensitivity. A dichroic ratio and short circuit current ratio of ≈6.1 and ≈1.6 were achieved, respectively.

  13. Processing Polarity Items: Contrastive Licensing Costs

    ERIC Educational Resources Information Center

    Saddy, Douglas; Drenhaus, Heiner; Frisch, Stefan

    2004-01-01

    We describe an experiment that investigated the failure to license polarity items in German using event-related brain potentials (ERPs). The results reveal distinct processing reflexes associated with failure to license positive polarity items in comparison to failure to license negative polarity items. Failure to license both negative and…

  14. Processing Polarity Items: Contrastive Licensing Costs

    ERIC Educational Resources Information Center

    Saddy, Douglas; Drenhaus, Heiner; Frisch, Stefan

    2004-01-01

    We describe an experiment that investigated the failure to license polarity items in German using event-related brain potentials (ERPs). The results reveal distinct processing reflexes associated with failure to license positive polarity items in comparison to failure to license negative polarity items. Failure to license both negative and…

  15. Processing polarity items: contrastive licensing costs.

    PubMed

    Saddy, Douglas; Drenhaus, Heiner; Frisch, Stefan

    2004-01-01

    We describe an experiment that investigated the failure to license polarity items in German using event-related brain potentials (ERPs). The results reveal distinct processing reflexes associated with failure to license positive polarity items in comparison to failure to license negative polarity items. Failure to license both negative and positive polarity items elicited an N400 component reflecting semantic integration cost. Failure to license positive polarity items, however, also elicited a P600 component. The additional P600 in the positive polarity violations may reflect higher processing complexity associated with a negative operator. This difference between the two types of violation suggests that the processing of negative and positive polarity items does not involve identical mechanisms.

  16. Microtubule polarity in the peripheral processes of trigeminal ganglion cells: relevance for the retrograde transport of herpes simplex virus.

    PubMed

    Topp, K S; Meade, L B; LaVail, J H

    1994-01-01

    The directional movement of many cellular organelles in neurons is dependent on polarized microtubules and direction-specific motor molecules. Microtubules are also thought to mediate the retrograde transport of herpes simplex virus (HSV) in sensory neurons. To define the cellular machinery responsible for retrograde axonal transport of HSV, we have investigated the polarity of microtubules in the peripheral axons of trigeminal ganglion neurons. The long ciliary nerves of rabbits were prepared for a standard "hook assay" of microtubule polarity. Axons in cross-sectioned nerves contained microtubules with almost uniform orientation. The fast-growing, plus ends of these axonal microtubules are located distal to the cell body and the slow-growing, minus ends are directed centrally. To determine the role played by microtubules in the retrograde transport of HSV in these axons, we injected the retrobulbar space of mice with the microtubule-inhibiting drugs colchicine, vinblastine, or nocodazole or with the microfilament inhibitor cytochalasin D and 1 d later inoculated the cornea with HSV. We found that colchicine, vinblastine, or nocodazole reduced by 52-87% the amount of virus recovered from the ganglion 3 d postinoculation, compared to vehicle-treated animals. In contrast, cytochalasin D or beta-lumicolchicine did not significantly reduce the amount of HSV recovered from the ganglion. We conclude that the retrograde axonal transport of HSV from axon endings in the cornea to the trigeminal ganglion cell bodies requires intact microtubules and occurs in a plus-to-minus direction on the microtubules. Our data are consistent with the hypothesis that the retrograde axonal transport of HSV is mediated by a minus end-directed motor molecule, for example, cytoplasmic dynein.

  17. Physical processes in spin polarized plasmas

    SciTech Connect

    Kulsrud, R.M.; Valeo, E.J.; Cowley, S.

    1984-05-01

    If the plasma in a nuclear fusion reactor is polarized, the nuclear reactions are modified in such a way as to enhance the reactor performance. We calculate in detail the modification of these nuclear reactions by different modes of polarization of the nuclear fuel. We also consider in detail the various physical processes that can lead to depolarization and show that they are by and large slow enough that a high degree of polarization can be maintained.

  18. Planar cell polarity and the kidney

    PubMed Central

    Papakrivopoulou, Eugenia; Dean, Charlotte H.; Copp, Andrew J.; Long, David A.

    2014-01-01

    Planar cell polarity (PCP) is the uniform orientation and alignment of a group of cells orthogonal to the apical–basal axis within a tissue. Originally described in insects, it is now known that PCP is required for many processes in vertebrates, including directional cell movement, polarized cell division, ciliary orientation, neural tube closure, heart development and lung branching. In this review, we outline the evidence implicating PCP in kidney development and disease focusing initially on the function of PCP in ureteric bud branching and elongation. We then describe how defects in PCP may lead to polycystic kidney disease and discuss a newly identified role for PCP in the kidney filtration barrier. PMID:24293657

  19. Exploring the inhibitory effect of membrane tension on cell polarization

    PubMed Central

    Wang, Jing; Yang, Gen; Ouyang, Qi; Wang, Yugang; Zhang, Lei

    2017-01-01

    Cell polarization toward an attractant is influenced by both physical and chemical factors. Most existing mathematical models are based on reaction-diffusion systems and only focus on the chemical process occurring during cell polarization. However, membrane tension has been shown to act as a long-range inhibitor of cell polarization. Here, we present a cell polarization model incorporating the interplay between Rac GTPase, filamentous actin (F-actin), and cell membrane tension. We further test the predictions of this model by performing single cell measurements of the spontaneous polarization of cancer stem cells (CSCs) and non-stem cancer cells (NSCCs), as the former have lower cell membrane tension. Based on both our model and the experimental results, cell polarization is more sensitive to stimuli under low membrane tension, and high membrane tension improves the robustness and stability of cell polarization such that polarization persists under random perturbations. Furthermore, our simulations are the first to recapitulate the experimental results described by Houk et al., revealing that aspiration (elevation of tension) and release (reduction of tension) result in a decrease in and recovery of the activity of Rac-GTP, respectively, and that the relaxation of tension induces new polarity of the cell body when a cell with the pseudopod-neck-body morphology is severed. PMID:28135277

  20. Multiscale View of Cytoskeletal Mechanoregulation of Cell and Tissue Polarity.

    PubMed

    Luxenburg, Chen; Geiger, Benjamin

    2017-01-01

    The ability of cells to generate, maintain, and repair tissues with complex architecture, in which distinct cells function as coherent units, relies on polarity cues. Polarity can be described as an asymmetry along a defined axis, manifested at the molecular, structural, and functional levels. Several types of cell and tissue polarities were described in the literature, including front-back, apical-basal, anterior-posterior, and left-right polarity. Extensive research provided insights into the specific regulators of each polarization process, as well as into generic elements that affect all types of polarities. The actin cytoskeleton and the associated adhesion structures are major regulators of most, if not all, known forms of polarity. Actin filaments exhibit intrinsic polarity and their ability to bind many proteins including the mechanosensitive adhesion and motor proteins, such as myosins, play key roles in cell polarization. The actin cytoskeleton can generate mechanical forces and together with the associated adhesions, probe the mechanical, structural, and chemical properties of the environment, and transmit signals that impact numerous biological processes, including cell polarity. In this article we highlight novel mechanisms whereby the mechanical forces and actin-adhesion complexes regulate cell and tissue polarity in a variety of natural and experimental systems.

  1. Cell Polarization and Cytokinesis in Budding Yeast

    PubMed Central

    Bi, Erfei; Park, Hay-Oak

    2012-01-01

    Asymmetric cell division, which includes cell polarization and cytokinesis, is essential for generating cell diversity during development. The budding yeast Saccharomyces cerevisiae reproduces by asymmetric cell division, and has thus served as an attractive model for unraveling the general principles of eukaryotic cell polarization and cytokinesis. Polarity development requires G-protein signaling, cytoskeletal polarization, and exocytosis, whereas cytokinesis requires concerted actions of a contractile actomyosin ring and targeted membrane deposition. In this chapter, we discuss the mechanics and spatial control of polarity development and cytokinesis, emphasizing the key concepts, mechanisms, and emerging questions in the field. PMID:22701052

  2. The interdependence of the Rho GTPases and apicobasal cell polarity

    PubMed Central

    Mack, Natalie Ann; Georgiou, Marios

    2014-01-01

    Signaling via the Rho GTPases provides crucial regulation of numerous cell polarization events, including apicobasal (AB) polarity, polarized cell migration, polarized cell division and neuronal polarity. Here we review the relationships between the Rho family GTPases and epithelial AB polarization events, focusing on the 3 best-characterized members: Rho, Rac and Cdc42. We discuss a multitude of processes that are important for AB polarization, including lumen formation, apical membrane specification, cell-cell junction assembly and maintenance, as well as tissue polarity. Our discussions aim to highlight the immensely complex regulatory mechanisms that encompass Rho GTPase signaling during AB polarization. More specifically, in this review we discuss several emerging common themes, that include: 1) the need for Rho GTPase activities to be carefully balanced in both a spatial and temporal manner through a multitude of mechanisms; 2) the existence of signaling feedback loops and crosstalk to create robust cellular responses; and 3) the frequent multifunctionality that exists among AB polarity regulators. Regarding this latter theme, we provide further discussion of the potential plasticity of the cell polarity machinery and as a result the possible implications for human disease. PMID:25469537

  3. Sterol-Rich Membrane Domains Define Fission Yeast Cell Polarity.

    PubMed

    Makushok, Tatyana; Alves, Paulo; Huisman, Stephen Michiel; Kijowski, Adam Rafal; Brunner, Damian

    2016-05-19

    Cell polarization is crucial for the functioning of all organisms. The cytoskeleton is central to the process but its role in symmetry breaking is poorly understood. We study cell polarization when fission yeast cells exit starvation. We show that the basis of polarity generation is de novo sterol biosynthesis, cell surface delivery of sterols, and their recruitment to the cell poles. This involves four phases occurring independent of the polarity factor cdc42p. Initially, multiple, randomly distributed sterol-rich membrane (SRM) domains form at the plasma membrane, independent of the cytoskeleton and cell growth. These domains provide platforms on which the growth and polarity machinery assembles. SRM domains are then polarized by the microtubule-dependent polarity factor tea1p, which prepares for monopolar growth initiation and later switching to bipolar growth. SRM polarization requires F-actin but not the F-actin organizing polarity factors for3p and bud6p. We conclude that SRMs are key to cell polarization.

  4. Cell polarity: netrin calms an excitable system.

    PubMed

    McClure, Allison W; Lew, Daniel J

    2014-11-03

    In a tractable model for cell invasion, the Caenorhabditis elegans anchor cell migrates through basement membranes towards a polarity cue provided by netrin. A new study reveals that the anchor cell polarity network can break symmetry and oscillate in the absence of netrin, suggesting the presence of interlinked positive and negative feedback loops, which are common in polarity pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Apicobasal polarity of brain endothelial cells

    PubMed Central

    Worzfeld, Thomas

    2015-01-01

    Normal brain homeostasis depends on the integrity of the blood–brain barrier that controls the access of nutrients, humoral factors, and immune cells to the CNS. The blood–brain barrier is composed mainly of brain endothelial cells. Forming the interface between two compartments, they are highly polarized. Apical/luminal and basolateral/abluminal membranes differ in their lipid and (glyco-)protein composition, allowing brain endothelial cells to secrete or transport soluble factors in a polarized manner and to maintain blood flow. Here, we summarize the basic concepts of apicobasal cell polarity in brain endothelial cells. To address potential molecular mechanisms underlying apicobasal polarity in brain endothelial cells, we draw on investigations in epithelial cells and discuss how polarity may go awry in neurological diseases. PMID:26661193

  6. Epithelial cell polarity determinant CRB3 in cancer development.

    PubMed

    Li, Pingping; Mao, Xiaona; Ren, Yu; Liu, Peijun

    2015-01-01

    Cell polarity, which is defined as asymmetry in cell shape, organelle distribution and cell function, is essential in numerous biological processes, including cell growth, cell migration and invasion, molecular transport, and cell fate. Epithelial cell polarity is mainly regulated by three conserved polarity protein complexes, the Crumbs (CRB) complex, partitioning defective (PAR) complex and Scribble (SCRIB) complex. Research evidence has indicated that dysregulation of cell polarity proteins may play an important role in cancer development. Crumbs homolog 3 (CRB3), a member of the CRB complex, may act as a cancer suppressor in mouse kidney epithelium and mouse mammary epithelium. In this review, we focus on the current data available on the roles of CRB3 in cancer development.

  7. Rho-GTPase-regulated vesicle trafficking in plant cell polarity.

    PubMed

    Chen, Xu; Friml, Jiří

    2014-02-01

    ROPs (Rho of plants) belong to a large family of plant-specific Rho-like small GTPases that function as essential molecular switches to control diverse cellular processes including cytoskeleton organization, cell polarization, cytokinesis, cell differentiation and vesicle trafficking. Although the machineries of vesicle trafficking and cell polarity in plants have been individually well addressed, how ROPs co-ordinate those processes is still largely unclear. Recent progress has been made towards an understanding of the co-ordination of ROP signalling and trafficking of PIN (PINFORMED) transporters for the plant hormone auxin in both root and leaf pavement cells. PIN transporters constantly shuttle between the endosomal compartments and the polar plasma membrane domains, therefore the modulation of PIN-dependent auxin transport between cells is a main developmental output of ROP-regulated vesicle trafficking. The present review focuses on these cellular mechanisms, especially the integration of ROP-based vesicle trafficking and plant cell polarity.

  8. [Cell polarity in the cardiovascular system].

    PubMed

    Haller, C; Kübler, W

    1999-05-01

    The importance of cell polarity as a fundamental biological principle is increasingly recognized in the cardiovascular system. Polar cell mechanisms underlie not only the development of the heart and blood vessels, but also play a major role in the adult organism for polarized endothelial functions such as the separation of the intra- and extravascular compartment and the vectorial exchange of substances between these compartments. Endothelial cells are connected through intercellular junctions which separate the functionally and structurally distinct luminal and abluminal cell surfaces. The luminal plasma membrane is in contact with the blood and takes part in the regulation of hemostasis. The abluminal cell membrane connects the endothelial cell with the basement membrane and modulates blood flow through the release of vasoactive substances. Results from epithelial model systems have shown that the polarized cell phenotype is generated by specific protein sorting and regulated protein trafficking between the trans-Golgi network and the cell surface. The polarized distribution of cell membrane proteins is maintained by anchorage with the cytoskeleton and limitation of lateral diffusion by tight junctions. Disturbances of cell polarity may contribute to the pathogenesis of disease states, including ischemic and radiocontrast-induced acute renal failure and carcinomas. Recent results have demonstrated the importance of cholesterol for protein traffic from the trans-Golgi network to the apical cell membrane. This novel intracellular function of cholesterol could point to a connection between cell polarity and the pathogenesis of arteriosclerosis. The polarity of the endothelium also has to be taken into account when developing gene-therapeutic strategies, since therapeutic success will not only depend on the efficient expression of the desired gene product, but also on its correct cellular location or secretion into the correct extracellular compartment. These

  9. Molecular mechanisms of membrane polarity in renal epithelial cells.

    PubMed

    Campo, C; Mason, A; Maouyo, D; Olsen, O; Yoo, D; Welling, P A

    2005-01-01

    Exciting discoveries in the last decade have cast light onto the fundamental mechanisms that underlie polarized trafficking in epithelial cells. It is now clear that epithelial cell membrane asymmetry is achieved by a combination of intracellular sorting operations, vectorial delivery mechanisms and plasmalemma-specific fusion and retention processes. Several well-defined signals that specify polarized segregation, sorting, or retention processes have, now, been described in a number of proteins. The intracellular machineries that decode and act on these signals are beginning to be described. In addition, the nature of the molecules that associate with intracellular trafficking vesicles to coordinate polarized delivery, tethering, docking, and fusion are also becoming understood. Combined with direct visualization of polarized sorting processes with new technologies in live-cell fluorescent microscopy, new and surprising insights into these once-elusive trafficking processes are emerging. Here we provide a review of these recent advances within an historically relevant context.

  10. Mixing processes within the polar night jet

    NASA Technical Reports Server (NTRS)

    Pierce, R. Bradley; Fairlie, T. Duncan; Grose, William L.; Swinbank, Richard; O'Neill, Alan

    1994-01-01

    Lagrangian material line simulations are performed using U.K. Meteorological Office simulated winds and temperatures to examine mixing processes in the middle- and lower-stratospheric polar night jet during the 1992 Southern Hemisphere spring and Northern Hemisphere winter. The Lagrangian simulations are undertaken to provide insight into the effects of mixing within the polar night jet on observations of the polar vortex made by instruments onboard the Upper Atmosphere Research Satellite (UARS) during these periods. A moderate to strong kinematic barrier to large-scale isentropic exchange, similar to the barrier identified in General Circulation Model (GCM) simulations, is identified during both of these periods. Characteristic timescales for mixing by large-scale isentropic motions within the polar night jet range from 20 days in the Southern Hemisphere lower stratosphere to years in the Northern Hemisphere middle stratosphere. The long mixing timescales found in the Northern Hemisphere polar night jet do not persist. Instead, the Northern Hemisphere kinematic barriers are broken down as part of the large-scale stratospheric response to a strong tropospheric blocking event. A series of Lagrangian experiments are conducted to investigate the sensitivity of the kinematic barrier to diabatic effects and to small-scale inertial gravity wave motions. Differential diabatic descent is found to have a significant impact on mixing processes within the Southern Hemisphere middle-stratospheric jet core. The interaction between small-scale displacements by idealized, inertial gravity waves and the large-scale flow is found to have a significant impact on mixing within the polar night jet in both hemispheres. These sensitivity experiments suggest that scales of motion that are unresolved in global assimilated datasets may contribute to mass exchange across the kinematic barrier to large-scale isentropic motion.

  11. Rebuilding cytoskeleton roads: Active-transport-induced polarization of cells

    NASA Astrophysics Data System (ADS)

    Hawkins, R. J.; Bénichou, O.; Piel, M.; Voituriez, R.

    2009-10-01

    Many cellular processes require a polarization axis which generally initially emerges as an inhomogeneous distribution of molecular markers in the cell. We present a simple analytical model of a general mechanism of cell polarization taking into account the positive feedback due to the coupled dynamics of molecular markers and cytoskeleton filaments. We find that the geometry of the organization of cytoskeleton filaments, nucleated on the membrane (e.g., cortical actin) or from a center in the cytoplasm (e.g., microtubule asters), dictates whether the system is capable of spontaneous polarization or polarizes only in response to external asymmetric signals. Our model also captures the main features of recent experiments of cell polarization in two considerably different biological systems, namely, mating budding yeast and neuron growth cones.

  12. International Polar Orbiter Processing Package (IPOPP)

    NASA Astrophysics Data System (ADS)

    Overton, J.; Fesenger, G.; Reed, B.; Thomas, W.

    2009-12-01

    In 1994, the United States merged its two polar-orbiting operational environmental satellite programs operated by the Department of Commerce and the Department of Defense respectively into a single system which is called the National Polar-orbiting Operational Environmental Satellite System (NPOESS). NPOESS is a tri-agency program comprised of the Department of Defense, the Department of Commerce and the National Aeronautics and Space Administration. NPOESS is managed by the Integrated Program Office (IPO) that is staffed by personnel from the three sponsoring agencies. The IPO is working with prime contractor Northrop Grumman Aerospace Systems (NGAS) and its subcontractors to develop, launch, and operate NPOESS. The first NPOESS satellite which is planned for 2013 will be preceded by a risk reduction mission named the NPOESS Preparatory Project (NPP) that is planned for launch in 2010. The International Polar Orbiter Processing Package (IPOPP) is a software package that will enable the Direct Readout user community to smoothly transition from the Earth Observing System (EOS) to the NPOESS. IPOPP will host US Government sanctioned algorithms that will enable the Direct Broadcast (DB) community to process, visualize, and evaluate Polar Orbiter Sensor and Environmental Data Records (starting with the Moderate Resolution Imaging Spectroradiometer (MODIS) and the NPP missions). The IPOPP development approach is to start with a framework that uses a Science Processing Algorithm (SPA) wrapping technique that allows a modular implementation to envelop sensor unique algorithms thus making IPOPP a multi-mission processing package. As a multi-platform processing package, IPOPP will meet the high expectations of the Direct Broadcast community for mission continuity from EOS to NPOESS, enable a global feedback loop for NPP Cal/Val campaigns, and initiate the role of the research to operations provider for the Direct Readout Mission.

  13. Cell polarity signaling in the plasticity of cancer cell invasiveness

    PubMed Central

    Gandalovičová, Aneta; Vomastek, Tomáš; Rosel, Daniel; Brábek, Jan

    2016-01-01

    Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness. PMID:26872368

  14. Cell polarity signaling in the plasticity of cancer cell invasiveness.

    PubMed

    Gandalovičová, Aneta; Vomastek, Tomáš; Rosel, Daniel; Brábek, Jan

    2016-05-03

    Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness.

  15. Orchestrating Lymphocyte Polarity in Cognate Immune Cell–Cell Interactions

    PubMed Central

    2016-01-01

    The immune synapse (IS) is a specialized structure established between different immune cells that fulfills several functions, including a role as a communication bridge. This intimate contact between a T cell and an antigen-presenting cell promotes the proliferation and differentiation of lymphocytes involved in the contact. T-cell activation requires the specific triggering of the T-cell receptor (TCR), which promotes the activation of different signaling pathways inducing the polarization of the T cell. During this process, different adhesion and signaling receptors reorganize at specialized membrane domains, concomitantly to the polarization of the tubulin and actin cytoskeletons, forming stable polarization platforms. The centrosome also moves toward the IS, driving the movement of different organelles, such as the biosynthetic, secretory, degrading machinery, and mitochondria, to sustain T-cell activation. A proper orchestration of all these events is essential for T-cell effector functions and the accomplishment of a complete immune response. PMID:27692176

  16. Does cell polarity matter during spermatogenesis?

    PubMed

    Gao, Ying; Cheng, C Yan

    2016-01-01

    Cell polarity is crucial to development since apico-basal polarity conferred by the 3 polarity protein modules (or complexes) is essential during embryogenesis, namely the Par (partition defective)-, the CRB (Crumbs)-, and the Scribble-based polarity protein modules. While these protein complexes and their component proteins have been extensively studied in Drosophila and C. elegans and also other mammalian tissues and/or cells, their presence and physiological significance in the testis remain unexplored until the first paper on the Par-based protein published in 2008. Since then, the Par-, the Scribble- and the CRB-based protein complexes and their component proteins in the testis have been studied. These proteins are known to confer Sertoli and spermatid polarity in the seminiferous epithelium, and they are also integrated components of the tight junction (TJ) and the basal ectoplasmic specialization (ES) at the Sertoli cell-cell interface near the basement membrane, which in turn constitute the blood-testis barrier (BTB). These proteins are also found at the apical ES at the Sertoli-spermatid interface. Thus, these polarity proteins also play a significant role in regulating Sertoli and spermatid adhesion in the testis through their actions on actin-based cytoskeletal function. Recent studies have shown that these polarity proteins are having antagonistic effects on the BTB integrity in which the Par6- and CRB3-based polarity complexes promotes the integrity of the Sertoli cell TJ-permeability barrier, whereas the Scribble-based complex promotes restructuring/remodeling of the Sertoli TJ-barrier function. Herein, we carefully evaluate these findings and provide a hypothetic model regarding their role in the testis in the context of the functions of these polarity proteins in other epithelia, so that better experiments can be designed in future studies to explore their significance in spermatogenesis.

  17. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties

  18. Planar cell polarity in vertebrate limb morphogenesis.

    PubMed

    Gao, Bo; Yang, Yingzi

    2013-08-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning, and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/planar cell polarity (PCP) pathway that controls uniformly polarized cell behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner.

  19. Planar Cell Polarity in vertebrate limb morphogenesis

    PubMed Central

    Gao, Bo; Yang, Yingzi

    2013-01-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/Planar Cell Polarity (PCP) pathway that controls uniformly polarized cellular behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner. PMID:23747034

  20. Search for Polarization Effects in the Antiproton Production Process

    DOE PAGES

    Grzonka, D.; Kilian, K.; Ritman, J.; ...

    2015-01-01

    For the production of a polarized antiproton beam, various methods have been suggested including the possibility that antiprotons may be produced polarized which will be checked experimentally. The polarization of antiprotons produced under typical conditions for antiproton beam preparation will be measured at the CERN/PS. If the production process creates some polarization, a polarized antiproton beam could be prepared by a rather simple modification of the antiproton beam facility. The detection setup and the expected experimental conditions are described.

  1. Search for Polarization Effects in the Antiproton Production Process

    SciTech Connect

    Grzonka, D.; Kilian, K.; Ritman, J.; Sefzick, T.; Oelert, W.; Diermaier, M.; Widmann, E.; Zmeskal, J.; Głowacz, B.; Moskal, P.; Zieliński, M.; Wolke, M.; Nadel-Turonski, P.; Carmignotto, M.; Horn, T.; Mkrtchyan, H.; Asaturyan, A.; Mkrtchyan, A.; Tadevosyan, V.; Zhamkochyan, S.; Malbrunot-Ettenauer, S.; Eyrich, W.; Hauenstein, F.; Zink, A.

    2015-01-01

    For the production of a polarized antiproton beam, various methods have been suggested including the possibility that antiprotons may be produced polarized which will be checked experimentally. The polarization of antiprotons produced under typical conditions for antiproton beam preparation will be measured at the CERN/PS. If the production process creates some polarization, a polarized antiproton beam could be prepared by a rather simple modification of the antiproton beam facility. The detection setup and the expected experimental conditions are described.

  2. Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity-signaling pathway.

    PubMed

    Guillabert-Gourgues, Aude; Jaspard-Vinassa, Beatrice; Bats, Marie-Lise; Sewduth, Raj N; Franzl, Nathalie; Peghaire, Claire; Jeanningros, Sylvie; Moreau, Catherine; Roux, Etienne; Larrieu-Lahargue, Frederic; Dufourcq, Pascale; Couffinhal, Thierry; Duplàa, Cecile

    2016-03-15

    Angiogenesis involves the coordinated growth and migration of endothelial cells (ECs) toward a proangiogenic signal. The Wnt planar cell polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl-associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization for oriented cell migration. Here we report that Kif26b--a kinesin--and Daam1 cooperatively regulate initiation of EC sprouting and directional migration via MT reorganization. First, we find that Kif26b is recruited within the Dvl3/Daam1 complex. Using a three-dimensional in vitro angiogenesis assay, we show that Kif26b and Daam1 depletion impairs tip cell polarization and destabilizes extended vascular processes. Kif26b depletion specifically alters EC directional migration and mislocalized MT organizing center (MTOC)/Golgi and myosin IIB cell rear enrichment. Therefore the cell fails to establish a proper front-rear polarity. Of interest, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we show that Kif26b functions in MT stabilization, which is indispensable for asymmetrical cell structure reorganization. These data demonstrate that Kif26b, together with Dvl3/Daam1, initiates cell polarity through the control of PCP signaling pathway-dependent activation.

  3. Polarization effects in Drell-Yan processes

    NASA Astrophysics Data System (ADS)

    Sissakian, A. N.; Shevchenko, O. Yu.; Nagaitsev, A. P.; Ivanov, O. N.

    2010-01-01

    Effects of polarization of hadrons and constituent quarks in Drell-Yan processes are considered; they are one of the most efficient tools for investigation of the quark structure of hadrons. Special attention is paid to such important parton distribution functions as the transversity and T-odd Sivers and Boer—Mulders functions whose study is necessary for understanding the effects connected with the nonzero transverse component of the quark momentum. An original method for direct extraction of transversity and Boer—Mulders function in the proton from the data on Drell—Yan processes, in which a maximum of one hadron in the initial state is transversely polarized, is presented. This method possesses a number of important advantages. The method is applied both to Drell—Yan processes with a valence antiquark (antiproton-proton and pion-proton collisions) and with a sea antiquark (proton-proton, proton-deuteron, and deuteron-deuteron collisions). Theoretical estimates of asymmetries and cross sections for setups at RHIC (BNL, US), NICA (JINR, Russia), COMPASS (CERN, Switzerland), PAX (GSI, Germany), and J-PARC (Japan) are presented for evaluation of the measurability of transversity and T-odd distributions. These theoretical estimates are accompanied by calculations of statistical uncertainties for measured asymmetries using the new Monte Carlo generator of Drell—Yan events. The duality of Drell—Yan processes and those of production of J/Φ resonance is studied, and it may allow one to considerably reduce statistical uncertainties of parton distributions. Kinematical conditions, for which this duality can be observed, are evaluated.

  4. Cell polarization in budding and fission yeasts.

    PubMed

    Martin, Sophie G; Arkowitz, Robert A

    2014-03-01

    Polarization is a fundamental cellular property, which is essential for the function of numerous cell types. Over the past three to four decades, research using the best-established yeast systems in cell biological research, Saccharomyces cerevisiae (or budding yeast) and Schizosaccharomyces pombe (or fission yeast), has brought to light fundamental principles governing the establishment and maintenance of a polarized, asymmetric state. These two organisms, though both ascomycetes, are evolutionarily very distant and exhibit distinct shapes and modes of growth. In this review, we compare and contrast the two systems. We first highlight common cell polarization pathways, detailing the contribution of Rho GTPases, the cytoskeleton, membrane trafficking, lipids, and protein scaffolds. We then contrast the major differences between the two organisms, describing their distinct strategies in growth site selection and growth zone dimensions and compartmentalization, which may be the basis for their distinct shapes. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  5. Cellular Polarization and Contractility in Collective Cell Migration

    NASA Astrophysics Data System (ADS)

    Utuje, Kazage J. Christophe; Notbohm, Jacob; Banerjee, Shiladitya; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P.; Fredberg, Jeffrey J.; Marchetti, M. Cristina

    Collective cell migration drives many biological processes such as metastasis, morphogenesis and wound healing. These coordinated motions are driven by active forces. The physical nature of these forces and the mechanisms by which they generate collective cell migration are still not fully understood. We have developed a minimum physical model of a cell monolayer as an elastic continuum whose deformation field is coupled to two internal degrees of freedom: the concentration of a chemical signal, controlling cell Contractility, and the polarization field controlling the direction of local cell motion. By combining theory with experiments, we show that these two internal variables account for the sloshing waves and the systematic deviations of the direction of cell polarization from that of local cell velocity observed in confined cell monolayers. KJCU and MCM were supported by the Simons Foundation.

  6. Module level solutions to solar cell polarization

    DOEpatents

    Xavier, Grace , Li; Bo, [San Jose, CA

    2012-05-29

    A solar cell module includes interconnected solar cells, a transparent cover over the front sides of the solar cells, and a backsheet on the backsides of the solar cells. The solar cell module includes an electrical insulator between the transparent cover and the front sides of the solar cells. An encapsulant protectively packages the solar cells. To prevent polarization, the insulator has resistance suitable to prevent charge from leaking from the front sides of the solar cells to other portions of the solar cell module by way of the transparent cover. The insulator may be attached (e.g., by coating) directly on an underside of the transparent cover or be a separate layer formed between layers of the encapsulant. The solar cells may be back junction solar cells.

  7. Modeling the Control of Planar Cell Polarity

    PubMed Central

    Axelrod, Jeffrey D.; Tomlin, Claire J.

    2016-01-01

    A growing list of medically important developmental defects and disease mechanisms can be traced to disruption of the Planar Cell Polarity (PCP) pathway. The PCP system polarizes cells in epithelial sheets along an axis orthogonal to their apical-basal axis. Studies in the fruitfly, Drosophila, have led to the concept of a modular system controlling PCP. The components of the PCP signaling modules, and the effector systems with which they interact, function together to produce emergent patterns. Experimental methods allow the manipulation of individual PCP signaling molecules in specified groups of cells; these interventions not only perturb the polarization of the targeted cells at a subcellular level, but also perturb patterns of polarity at the multicellular level, often affecting nearby cells in characteristic ways. These kinds of experiments should, in principle, allow one to infer the architecture within and between modules, but the relationships between molecular interactions and tissue-level pattern are sufficiently complex that they defy intuitive understanding. Mathematical modeling has been an important tool to address these problems. This review explores the emergence of a local signaling hypothesis, and describes how a local intercellular signal, coupled with a directional cue, can give rise to global pattern. We will discuss the critical role mathematical modeling has played in guiding and interpreting experimental results, and speculate about future roles for mathematical modeling of PCP. Mathematical models at varying levels of abstraction have and are expected to continue contributing in distinct ways to understanding the regulation of PCP signaling. PMID:21755606

  8. Coordinated process of polarized growth in filamentous fungi.

    PubMed

    Takeshita, Norio

    2016-09-01

    Filamentous fungi are extremely polarized organisms, exhibiting continuous growth at their hyphal tips. The hyphal form is related to their pathogenicity in animals and plants, and their high secretion ability for biotechnology. Polarized growth requires a sequential supply of proteins and lipids to the hyphal tip. This transport is managed by vesicle trafficking via the actin and microtubule cytoskeleton. Therefore, the arrangement of the cytoskeleton is a crucial step to establish and maintain the cell polarity. This review summarizes recent findings unraveling the mechanism of polarized growth with special emphasis on the role of actin and microtubule cytoskeleton and polarity marker proteins. Rapid insertions of membranes via highly active exocytosis at hyphal tips could quickly dilute the accumulated polarity marker proteins. Recent findings by a super-resolution microscopy indicate that filamentous fungal cells maintain their polarity at the tips by repeating transient assembly and disassembly of polarity sites.

  9. Cell polarity in plants: when two do the same, it is not the same....

    PubMed

    Dettmer, Jan; Friml, Jiří

    2011-12-01

    In unicellular and multicellular organisms, cell polarity is essential for a wide range of biological processes. An important feature of cell polarity is the asymmetric distribution of proteins in or at the plasma membrane. In plants such polar localized proteins play various specific roles ranging from organizing cell morphogenesis, asymmetric cell division, pathogen defense, nutrient transport and establishment of hormone gradients for developmental patterning. Moreover, flexible respecification of cell polarities enables plants to adjust their physiology and development to environmental changes. Having evolved multicellularity independently and lacking major cell polarity mechanisms of animal cells, plants came up with alternative solutions to generate and respecify cell polarity as well as to regulate polar domains at the plasma membrane.

  10. Development and dynamics of cell polarity at a glance.

    PubMed

    Campanale, Joseph P; Sun, Thomas Y; Montell, Denise J

    2017-04-01

    Cells exhibit morphological and molecular asymmetries that are broadly categorized as cell polarity. The cell polarity established in early embryos prefigures the macroscopic anatomical asymmetries characteristic of adult animals. For example, eggs and early embryos have polarized distributions of RNAs and proteins that generate global anterior/posterior and dorsal/ventral axes. The molecular programs that polarize embryos are subsequently reused in multiple contexts. Epithelial cells require apical/basal polarity to establish their barrier function. Migrating cells polarize in the direction of movement, creating distinct leading and trailing structures. Asymmetrically dividing stem cells partition different molecules between themselves and their daughter cells. Cell polarity can develop de novo, be maintained through rounds of cell division and be dynamically remodeled. In this Cell Science at a Glance review and poster, we describe molecular asymmetries that underlie cell polarity in several cellular contexts. We highlight multiple developmental systems that first establish cell/developmental polarity, and then maintain it. Our poster showcases repeated use of the Par, Scribble and Crumbs polarity complexes, which drive the development of cell polarity in many cell types and organisms. We then briefly discuss the diverse and dynamic changes in cell polarity that occur during cell migration, asymmetric cell division and in planar polarized tissues.

  11. Planar cell polarity (PCP) proteins and spermatogenesis.

    PubMed

    Chen, Haiqi; Cheng, C Yan

    2016-11-01

    In adult mammalian testes, spermatogenesis is comprised of several discrete cellular events that work in tandem to support the transformation and differentiation of diploid spermatogonia to haploid spermatids in the seminiferous epithelium during the seminiferous epithelial cycle. These include: self-renewal of spermatogonial stem cells via mitosis and their transformation into differentiated spermatogonia, meiosis I/II, spermiogenesis and the release of sperms at spermiation. Studies have shown that these cellular events are under precise and coordinated controls of multiple proteins and signaling pathways. These events are also regulated by polarity proteins that are known to confer classical apico-basal (A/B) polarity in other epithelia. Furthermore, spermatid development is likely supported by planar cell polarity (PCP) proteins since polarized spermatids are aligned across the plane of seminiferous epithelium in an orderly fashion, analogous to hair cells in the cochlea of the inner ear. Thus, the maximal number of spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes. In this review, we briefly summarize recent findings regarding the role of PCP proteins in the testis. This information should be helpful in future studies to better understand the role of PCP proteins in spermatogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Retinal Processing: Polarization Vision in Teleost Fishes

    DTIC Science & Technology

    2005-07-26

    an exciting opportunity to study retinal structure and function as it pertains to polarization vision. For example, salmon and coral reef fishes both...polarization sensitivity in three species of coral reef fishes commonly known as damselfishes. Here we show that three species of damselfishes (three-spot...conspecific visual communication network utilizing polarized light signals in the coral reef environment. These observations have provoked interest in the

  13. ROS Regulation of Polar Growth in Plant Cells1[OPEN

    PubMed Central

    Mangano, Silvina; Juárez, Silvina Paola Denita

    2016-01-01

    Root hair cells and pollen tubes, like fungal hyphae, possess a typical tip or polar cell expansion with growth limited to the apical dome. Cell expansion needs to be carefully regulated to produce a correct shape and size. Polar cell growth is sustained by oscillatory feedback loops comprising three main components that together play an important role regulating this process. One of the main components are reactive oxygen species (ROS) that, together with calcium ions (Ca2+) and pH, sustain polar growth over time. Apoplastic ROS homeostasis controlled by NADPH oxidases as well as by secreted type III peroxidases has a great impact on cell wall properties during cell expansion. Polar growth needs to balance a focused secretion of new materials in an extending but still rigid cell wall in order to contain turgor pressure. In this review, we discuss the gaps in our understanding of how ROS impact on the oscillatory Ca2+ and pH signatures that, coordinately, allow root hair cells and pollen tubes to expand in a controlled manner to several hundred times their original size toward specific signals. PMID:27208283

  14. ROS Regulation of Polar Growth in Plant Cells.

    PubMed

    Mangano, Silvina; Juárez, Silvina Paola Denita; Estevez, José M

    2016-07-01

    Root hair cells and pollen tubes, like fungal hyphae, possess a typical tip or polar cell expansion with growth limited to the apical dome. Cell expansion needs to be carefully regulated to produce a correct shape and size. Polar cell growth is sustained by oscillatory feedback loops comprising three main components that together play an important role regulating this process. One of the main components are reactive oxygen species (ROS) that, together with calcium ions (Ca(2+)) and pH, sustain polar growth over time. Apoplastic ROS homeostasis controlled by NADPH oxidases as well as by secreted type III peroxidases has a great impact on cell wall properties during cell expansion. Polar growth needs to balance a focused secretion of new materials in an extending but still rigid cell wall in order to contain turgor pressure. In this review, we discuss the gaps in our understanding of how ROS impact on the oscillatory Ca(2+) and pH signatures that, coordinately, allow root hair cells and pollen tubes to expand in a controlled manner to several hundred times their original size toward specific signals. © 2016 American Society of Plant Biologists. All Rights Reserved.

  15. Wnt proteins can direct planar cell polarity in vertebrate ectoderm

    PubMed Central

    Chu, Chih-Wen; Sokol, Sergei Y

    2016-01-01

    The coordinated orientation of cells across the tissue plane, known as planar cell polarity (PCP), is manifested by the segregation of core PCP proteins to different sides of the cell. Secreted Wnt ligands are involved in many PCP-dependent processes, yet whether they act as polarity cues has been controversial. We show that in Xenopus early ectoderm, the Prickle3/Vangl2 complex was polarized to anterior cell edges and this polarity was disrupted by several Wnt antagonists. In midgastrula embryos, Wnt5a, Wnt11, and Wnt11b, but not Wnt3a, acted across many cell diameters to orient Prickle3/Vangl2 complexes away from their sources regardless of their positions relative to the body axis. The planar polarity of endogenous Vangl2 in the neuroectoderm was similarly redirected by an ectopic Wnt source and disrupted after depletion of Wnt11b in the presumptive posterior region of the embryo. These observations provide evidence for the instructive role of Wnt ligands in vertebrate PCP. DOI: http://dx.doi.org/10.7554/eLife.16463.001 PMID:27658614

  16. Process control system using polarizing interferometer

    DOEpatents

    Schultz, Thomas J.; Kotidis, Petros A.; Woodroffe, Jaime A.; Rostler, Peter S.

    1994-01-01

    A system for non-destructively measuring an object and controlling industrial processes in response to the measurement is disclosed in which an impulse laser generates a plurality of sound waves over timed increments in an object. A polarizing interferometer is used to measure surface movement of the object caused by the sound waves and sensed by phase shifts in the signal beam. A photon multiplier senses the phase shift and develops an electrical signal. A signal conditioning arrangement modifies the electrical signals to generate an average signal correlated to the sound waves which in turn is correlated to a physical or metallurgical property of the object, such as temperature, which property may then be used to control the process. External, random vibrations of the workpiece are utilized to develop discernible signals which can be sensed in the interferometer by only one photon multiplier. In addition the interferometer includes an arrangement for optimizing its sensitivity so that movement attributed to various waves can be detected in opaque objects. The interferometer also includes a mechanism for sensing objects with rough surfaces which produce speckle light patterns. Finally the interferometer per se, with the addition of a second photon multiplier is capable of accurately recording beam length distance differences with only one reading.

  17. Process control system using polarizing interferometer

    DOEpatents

    Schultz, T.J.; Kotidis, P.A.; Woodroffe, J.A.; Rostler, P.S.

    1994-02-15

    A system for nondestructively measuring an object and controlling industrial processes in response to the measurement is disclosed in which an impulse laser generates a plurality of sound waves over timed increments in an object. A polarizing interferometer is used to measure surface movement of the object caused by the sound waves and sensed by phase shifts in the signal beam. A photon multiplier senses the phase shift and develops an electrical signal. A signal conditioning arrangement modifies the electrical signals to generate an average signal correlated to the sound waves which in turn is correlated to a physical or metallurgical property of the object, such as temperature, which property may then be used to control the process. External, random vibrations of the workpiece are utilized to develop discernible signals which can be sensed in the interferometer by only one photon multiplier. In addition the interferometer includes an arrangement for optimizing its sensitivity so that movement attributed to various waves can be detected in opaque objects. The interferometer also includes a mechanism for sensing objects with rough surfaces which produce speckle light patterns. Finally the interferometer per se, with the addition of a second photon multiplier is capable of accurately recording beam length distance differences with only one reading. 38 figures.

  18. Processing polarity: ERP evidence for differences between positive and negative polarity.

    PubMed

    Yurchenko, Anna; den Ouden, Dirk-Bart; Hoeksema, Jack; Dragoy, Olga; Hoeks, John C J; Stowe, Laurie A

    2013-01-01

    The goal of the present study was to investigate event-related potential (ERP) responses to Dutch negative and positive polarity adverbs of degree presented in licensed and unlicensed contexts with negative and affirmative particles directly preceding the polarity item. To control for effects of the processing of negation as such, neutral adverbs were also presented in negative and affirmative contexts. The results did not show any significant effect of negation for the non-polar adverbs, allowing context effects for polarity items to be interpreted as being due to the appropriateness of the context. Negative polarity violations elicited an N400 response that might reflect the lack of semantic congruity of the negative polarity item in an affirmative context. In contrast, processing positive polarity items in context of negation resulted in a positive effect resembling the P600, which may be considered as a marker of a different sort of integration difficulty caused by violation of licensing conditions and/or a search for a licensor in the wider discourse context. The study presented here is the first to show an unambiguous dissociation between responses to negative and positive polarity violations. This dissociation argues for different mechanisms underlying the processing of these two types of polarity; we propose that positive polarity items are sensitive to wider discourse context, while negative polarity items are more sensitive to local lexical context. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Moonlighting Motors: Kinesin, Dynein, and Cell Polarity.

    PubMed

    Lu, Wen; Gelfand, Vladimir I

    2017-03-08

    In addition to their well-known role in transporting cargoes in the cytoplasm, microtubule motors organize their own tracks - the microtubules. While this function is mostly studied in the context of cell division, it is essential for microtubule organization and generation of cell polarity in interphase cells. Kinesin-1, the most abundant microtubule motor, plays a role in the initial formation of neurites. This review describes the mechanism of kinesin-1-driven microtubule sliding and discusses its biological significance in neurons. Recent studies describing the interplay between kinesin-1 and cytoplasmic dynein in the translocation of microtubules are discussed. In addition, we evaluate recent work exploring the developmental regulation of microtubule sliding during axonal outgrowth and regeneration. Collectively, the discussed works suggest that sliding of interphase microtubules by motors is a novel force-generating mechanism that reorganizes the cytoskeleton and drives shape change and polarization.

  20. Physical processes in polar stratospheric ice clouds

    NASA Technical Reports Server (NTRS)

    Toon, Owen B.; Turco, Richard; Jordan, Joseph

    1988-01-01

    A one dimensional model of cloud microphysics was used to simulate the formation and evolution of polar stratospheric ice clouds. Some of the processes which are included in the model are outlined. It is found that the clouds must undergo preferential nucleation upon the existing aerosols just as do tropospheric cirrus clouds. Therefore, there is an energy barrier between stratospheric nitric acid particles and ice particles implying that nitric acid does not form a continuous set of solutions between the trihydrate and ice. The Kelvin barrier is not significant in controlling the rate of formation of ice particles. It was found that the cloud properties are sensitive to the rate at which the air parcels cool. In wave clouds, with cooling rates of hundreds of degrees per day, most of the existing aerosols nucleate and become ice particles. Such clouds have particles with sizes on the order of a few microns, optical depths on order of unity and are probably not efficient at removing materials from the stratosphere. In clouds which form with cooling rates of a few degrees per day or less, only a small fraction of the aerosols become cloud particles. In such clouds the particle radius is larger than 10 microns, the optical depths are low and water vapor is efficiently removed. Seasonal simulations show that the lowest water vapor mixing ratio is determined by the lowest temperature reached, and that the time when clouds disappear is controlled by the time when temperatures begin to rise above the minimum values.

  1. Physical mechanisms redirecting cell polarity and cell shape

    PubMed Central

    Terenna, Courtney R.; Makushok, Tatyana; Velve-Casquillas, Guilhem; Baigl, Damien; Chen, Yong; Bornens, Michel; Paoletti, Anne; Piel, Matthieu; Tran, Phong T.

    2010-01-01

    Summary The fission yeast Schizosaccharomyces pombe has a cylindrical rod-shape that is organized and maintained by interactions between the microtubule, cell membrane, and actin cytoskeleton; i.e., microtubules deliver factors to the cell tips that subsequently recruit the actin machinery to direct localized cell growth [1]. Mutations affecting any components in this pathway lead to bent, branched, or round cells [2]. In this context, the cytoskeleton controls cell polarity and thus dictates cell shape. Here, we use soft-lithography techniques to construct microfluidic channels in order to control the shape of cells. We show that by physically forcing wildtype rod-shaped cells to grow bent, they will re-organize their cytoskeleton and re-direct cell polarity to make new ectopic cell tips. In addition, by physically forcing bent or round mutant cells to conform to the wildtype rod-shape, cells will reverse their mutational phenotypes by re-organizing their cytoskeleton to maintain proper wildtype-like microtubule, cell membrane proteins, and actin localizations. Our study provides direct evidence that the cytoskeleton controls cell polarity and cell shape and demonstrates that cell shape also controls the organization of the cytoskeleton, in a feedback loop. We present a model of the feedback loop which explains how fission yeast cells maintain a rod-shape, and how perturbation of specific parameters of the loop can lead to different cell shapes. PMID:19026544

  2. GTPases in bacterial cell polarity and signalling.

    PubMed

    Bulyha, Iryna; Hot, Edina; Huntley, Stuart; Søgaard-Andersen, Lotte

    2011-12-01

    In bacteria, large G domain GTPases have well-established functions in translation, protein translocation, tRNA modification and ribosome assembly. In addition, bacteria also contain small Ras-like GTPases consisting of stand-alone G domains. Recent data have revealed that small Ras-like GTPases as well as large G domain GTPases in bacteria function in the regulation of cell polarity, signal transduction and possibly also in cell division. The small Ras-like GTPase MglA together with its cognate GAP MglB regulates cell polarity in Myxococcus xanthus, and the small Ras-like GTPase CvnD9 in Streptomyces coelicolor is involved in signal transduction. Similarly, the large GTPase FlhF together with the ATPase FlhG regulates the localization and number of flagella in polarly flagellated bacteria. Moreover, large dynamin-like GTPases in bacteria may function in cell division. Thus, the function of GTPases in bacteria may be as pervasive as in eukaryotes.

  3. Pronephric Tubulogenesis Requires Daam1-Mediated Planar Cell Polarity Signaling

    PubMed Central

    Gomez de la Torre Canny, Sol; Jang, Chuan-Wei; Cho, Kyucheol; Ji, Hong; Wagner, Daniel S.; Jones, Elizabeth A.; Habas, Raymond

    2011-01-01

    Canonical β-catenin-mediated Wnt signaling is essential for the induction of nephron development. Noncanonical Wnt/planar cell polarity (PCP) pathways contribute to processes such as cell polarization and cytoskeletal modulation in several tissues. Although PCP components likely establish the plane of polarization in kidney tubulogenesis, whether PCP effectors directly modulate the actin cytoskeleton in tubulogenesis is unknown. Here, we investigated the roles of Wnt PCP components in cytoskeletal assembly during kidney tubule morphogenesis in Xenopus laevis and zebrafish. We found that during tubulogenesis, the developing pronephric anlagen expresses Daam1 and its interacting Rho-GEF (WGEF), which compose one PCP/noncanonical Wnt pathway branch. Knockdown of Daam1 resulted in reduced expression of late pronephric epithelial markers with no apparent effect upon early markers of patterning and determination. Inhibiting various points in the Daam1 signaling pathway significantly reduced pronephric tubulogenesis. These data indicate that pronephric tubulogenesis requires the Daam1/WGEF/Rho PCP pathway. PMID:21804089

  4. Anisotropy of cell adhesive microenvironment governs cell internal organization and orientation of polarity

    PubMed Central

    Théry, Manuel; Racine, Victor; Piel, Matthieu; Pépin, Anne; Dimitrov, Ariane; Chen, Yong; Sibarita, Jean-Baptiste; Bornens, Michel

    2006-01-01

    Control of the establishment of cell polarity is an essential function in tissue morphogenesis and renewal that depends on spatial cues provided by the extracellular environment. The molecular role of cell–cell or cell–extracellular matrix (ECM) contacts on the establishment of cell polarity has been well characterized. It has been hypothesized that the geometry of the cell adhesive microenvironment was directing cell surface polarization and internal organization. To define how the extracellular environment affects cell polarity, we analyzed the organization of individual cells plated on defined micropatterned substrates imposing cells to spread on various combinations of adhesive and nonadhesive areas. The reproducible normalization effect on overall cell compartmentalization enabled quantification of the spatial organization of the actin network and associated proteins, the spatial distribution of microtubules, and the positioning of nucleus, centrosome, and Golgi apparatus. By using specific micropatterns and statistical analysis of cell compartment positions, we demonstrated that ECM geometry determines the orientation of cell polarity axes. The nucleus–centrosome orientations were reproducibly directed toward cell adhesive edges. The anisotropy of the cell cortex in response to the adhesive conditions did not affect the centrosome positioning at the cell centroid. Based on the quantification of microtubule plus end distribution we propose a working model that accounts for that observation. We conclude that, in addition to molecular composition and mechanical properties, ECM geometry plays a key role in developmental processes. PMID:17179050

  5. Mechanical Checkpoint For Persistent Cell Polarization In Adhesion-Naive Fibroblasts

    PubMed Central

    Bun, Philippe; Liu, JunJun; Turlier, Hervé; Liu, ZengZhen; Uriot, Karen; Joanny, Jean-François; Coppey-Moisan, Maïté

    2014-01-01

    Cell polarization is a fundamental biological process implicated in nearly every aspect of multicellular development. The role of cell-extracellular matrix contacts in the establishment and the orientation of cell polarity have been extensively studied. However, the respective contributions of substrate mechanics and biochemistry remain unclear. Here we propose a believed novel single-cell approach to assess the minimal polarization trigger. Using nonadhered round fibroblast cells, we show that stiffness sensing through single localized integrin-mediated cues are necessary and sufficient to trigger and direct a shape polarization. In addition, the traction force developed by cells has to reach a minimal threshold of 56 ± 1.6 pN for persistent polarization. The polarization kinetics increases with the stiffness of the cue. The polarized state is characterized by cortical actomyosin redistribution together with cell shape change. We develop a physical model supporting the idea that a local and persistent inhibition of actin polymerization and/or myosin activity is sufficient to trigger and sustain the polarized state. Finally, the cortical polarity propagates to an intracellular polarity, evidenced by the reorientation of the centrosome. Our results define the minimal adhesive requirements and quantify the mechanical checkpoint for persistent cell shape and organelle polarization, which are critical regulators of tissue and cell development. PMID:25028874

  6. Planar cell polarity and the kidney.

    PubMed

    McNeill, Helen

    2009-10-01

    Planar cell polarity (PCP) is a form of spatial organization in tissue that was first described in Drosophila melanogaster. PCP plays a critical conserved role in several aspects of mammalian development. Exciting data implicate PCP in normal kidney development and suggest the loss of oriented cell division and convergent extension downstream of defective PCP signaling lead to cystic kidney disease in mouse models. In this review, I first cover the current knowledge of PCP signaling in invertebrate and vertebrate models and then explore how loss of PCP might underlie some forms of cystic kidney disease.

  7. Prenylation is required for polar cell elongation, cell adhesion, and differentiation in Physcomitrella patens.

    PubMed

    Thole, Julie M; Perroud, Pierre-Francois; Quatrano, Ralph S; Running, Mark P

    2014-05-01

    Protein prenylation is required for a variety of growth and developmental processes in flowering plants. Here we report the consequences of loss of function of all known prenylation subunits in the moss Physcomitrella patens. As in Arabidopsis, protein farnesyltransferase and protein geranylgeranyltransferase type I are not required for viability. However, protein geranylgeranyltransferase type I activity is required for cell adhesion, polar cell elongation, and cell differentiation. Loss of protein geranylgeranyltransferase activity results in colonies of round, single-celled organisms that resemble unicellular algae. The loss of protein farnesylation is not as severe but also results in polar cell elongation and differentiation defects. The complete loss of Rab geranylgeranyltransferase activity appears to be lethal in P. patens. Labeling with antibodies to cell wall components support the lack of polarity establishment and the undifferentiated state of geranylgeranyltransferase type I mutant plants. Our results show that prenylated proteins play key roles in P. patens development and differentiation processes.

  8. Control of cell polarity in response to intra- and extracellular signals in budding yeast.

    PubMed

    Knaus, Michele; Wiget, Philippe; Shimada, Yukiko; Peter, Matthias

    2005-01-01

    Budding yeast serves as a powerful genetic model organism for studying the molecular mechanisms of cell polarity in single cells. Like other polarized eukaryotic cells, yeast cells possess polarity programs that regulate where they grow and divide. Establishment of a site of cell polarity may be conceptualized in several stages. First, cells mark a specific location at the cell surface for polarized cell growth and cell division. To define these sites, cells use intrinsic cues present in the cell or landmarks determined by extracellular signals such as morphogens. Second, these landmark proteins then recruit or activate polarity establishment proteins including small GTPases and their regulators. Positive and negative feedback mechanisms are required to transform these site-selection processes into a stable axis of polarity. Finally, these locally activated GTPase modules recruit and activate proteins that organize the actin cytoskeleton and cell growth. In this short review, we describe molecular pathways required to establish oriented cell polarity, and emphasize recent advances in defining positive and negative feedback mechanisms that together may translate an initially weak symmetry-breaking signal into a robust axis of polarity.

  9. Functional genomics in the study of yeast cell polarity: moving in the right direction

    PubMed Central

    Styles, Erin; Youn, Ji-Young; Mattiazzi Usaj, Mojca; Andrews, Brenda

    2013-01-01

    The budding yeast Saccharomyces cerevisiae has been used extensively for the study of cell polarity, owing to both its experimental tractability and the high conservation of cell polarity and other basic biological processes among eukaryotes. The budding yeast has also served as a pioneer model organism for virtually all genome-scale approaches, including functional genomics, which aims to define gene function and biological pathways systematically through the analysis of high-throughput experimental data. Here, we outline the contributions of functional genomics and high-throughput methodologies to the study of cell polarity in the budding yeast. We integrate data from published genetic screens that use a variety of functional genomics approaches to query different aspects of polarity. Our integrated dataset is enriched for polarity processes, as well as some processes that are not intrinsically linked to cell polarity, and may provide new areas for future study. PMID:24062589

  10. Functional genomics in the study of yeast cell polarity: moving in the right direction.

    PubMed

    Styles, Erin; Youn, Ji-Young; Mattiazzi Usaj, Mojca; Andrews, Brenda

    2013-01-01

    The budding yeast Saccharomyces cerevisiae has been used extensively for the study of cell polarity, owing to both its experimental tractability and the high conservation of cell polarity and other basic biological processes among eukaryotes. The budding yeast has also served as a pioneer model organism for virtually all genome-scale approaches, including functional genomics, which aims to define gene function and biological pathways systematically through the analysis of high-throughput experimental data. Here, we outline the contributions of functional genomics and high-throughput methodologies to the study of cell polarity in the budding yeast. We integrate data from published genetic screens that use a variety of functional genomics approaches to query different aspects of polarity. Our integrated dataset is enriched for polarity processes, as well as some processes that are not intrinsically linked to cell polarity, and may provide new areas for future study.

  11. Dielectric structure of cells indicated from dc polarization methods

    NASA Astrophysics Data System (ADS)

    Barsamian, S. T.; Thornton, B. S.

    1985-02-01

    Electric polarization measurements on calf thymus cells show the existence of recently predicted dielectric zones which develop progressively within whole living cells when transforming from normal to tumourous.

  12. Mechanosensitive store-operated calcium entry regulates the formation of cell polarity.

    PubMed

    Huang, Yi-Wei; Chang, Shu-Jing; I-Chen Harn, Hans; Huang, Hui-Ting; Lin, Hsi-Hui; Shen, Meng-Ru; Tang, Ming-Jer; Chiu, Wen-Tai

    2015-09-01

    Ca(2+) -mediated formation of cell polarity is essential for directional migration which plays an important role in physiological and pathological processes in organisms. To examine the critical role of store-operated Ca(2+) entry, which is the major form of extracellular Ca(2+) influx in non-excitable cells, in the formation of cell polarity, we employed human bone osteosarcoma U2OS cells, which exhibit distinct morphological polarity during directional migration. Our analyses showed that Ca(2+) was concentrated at the rear end of cells and that extracellular Ca(2+) influx was important for cell polarization. Inhibition of store-operated Ca(2+) entry using specific inhibitors disrupted the formation of cell polarity in a dose-dependent manner. Moreover, the channelosomal components caveolin-1, TRPC1, and Orai1 were concentrated at the rear end of polarized cells. Knockdown of TRPC1 or a TRPC inhibitor, but not knockdown of Orai1, reduced cell polarization. Furthermore, disruption of lipid rafts or overexpression of caveolin-1 contributed to the downregulation of cell polarity. On the other hand, we also found that cell polarity, store-operated Ca(2+) entry activity, and cell stiffness were markedly decreased by low substrate rigidity, which may be caused by the disorganization of actin filaments and microtubules that occurs while regulating the activity of the mechanosensitive TRPC1 channel.

  13. The planar polarity pathway promotes coordinated cell migration during Drosophila oogenesis

    PubMed Central

    Bastock, Rebecca; Strutt, David

    2007-01-01

    SUMMARY Cell migration is fundamental in both animal morphogenesis and disease. The migration of individual cells is relatively well-studied, however in vivo cells often remain joined by cell-cell junctions and migrate in cohesive groups. How such groups of cells coordinate their migration is poorly understood. The planar polarity pathway coordinates the polarity of non-migrating cells in epithelial sheets and is required for cell rearrangements during vertebrate morphogenesis. It is therefore a good candidate to play a role in collective migration of groups of cells. Drosophila border cell migration is a well-characterised and genetically tractable model of collective cell migration, during which a group of about 6-10 epithelial cells detaches from the anterior end of the developing egg chamber and migrates invasively towards the oocyte. We find that the planar polarity pathway promotes this invasive migration, acting both in the migrating cells themselves and in the non-migratory polar follicle cells they carry along. Disruption of planar polarity signalling causes abnormalities in actin rich processes on the cell surface and leads to less efficient migration. This is apparently due in part to loss of regulation of Rho GTPase activity by the planar polarity receptor Frizzled, which itself becomes localised to the migratory edge of the border cells. We conclude that during collective cell migration the planar polarity pathway can mediate communication between motile and non-motile cells, which enhances the efficiency of migration via the modulation of actin dynamics. PMID:17652348

  14. The planar polarity pathway promotes coordinated cell migration during Drosophila oogenesis.

    PubMed

    Bastock, Rebecca; Strutt, David

    2007-09-01

    Cell migration is fundamental in both animal morphogenesis and disease. The migration of individual cells is relatively well-studied; however, in vivo, cells often remain joined by cell-cell junctions and migrate in cohesive groups. How such groups of cells coordinate their migration is poorly understood. The planar polarity pathway coordinates the polarity of non-migrating cells in epithelial sheets and is required for cell rearrangements during vertebrate morphogenesis. It is therefore a good candidate to play a role in the collective migration of groups of cells. Drosophila border cell migration is a well-characterised and genetically tractable model of collective cell migration, during which a group of about six to ten epithelial cells detaches from the anterior end of the developing egg chamber and migrates invasively towards the oocyte. We find that the planar polarity pathway promotes this invasive migration, acting both in the migrating cells themselves and in the non-migratory polar follicle cells that they carry along. Disruption of planar polarity signalling causes abnormalities in actin-rich processes on the cell surface and leads to less-efficient migration. This is apparently due, in part, to a loss of regulation of Rho GTPase activity by the planar polarity receptor Frizzled, which itself becomes localised to the migratory edge of the border cells. We conclude that, during collective cell migration, the planar polarity pathway can mediate communication between motile and non-motile cells, which enhances the efficiency of migration via the modulation of actin dynamics.

  15. Organizer activity of the polar cells during Drosophila oogenesis.

    PubMed

    Grammont, Muriel; Irvine, Kenneth D

    2002-11-01

    Patterning of the Drosophila egg requires the establishment of several distinct types of somatic follicle cells, as well as interactions between these follicle cells and the oocyte. The polar cells occupy the termini of the follicle and are specified by the activation of Notch. We have investigated their role in follicle patterning by creating clones of cells mutant for the Notch modulator fringe. This genetic ablation of polar cells results in cell fate defects within surrounding follicle cells. At the anterior, the border cells, the immediately adjacent follicle cell fate, are absent, as are the more distant stretched and centripetal follicle cells. Conversely, increasing the number of polar cells by expressing an activated form of the Notch receptor increases the number of border cells. At the posterior, elimination of polar cells results in abnormal oocyte localization. Moreover, when polar cells are mislocalized laterally, the surrounding follicle cells adopt a posterior fate, the oocyte is located adjacent to them, and the anteroposterior axis of the oocyte is re-oriented with respect to the ectopic polar cells. Our observations demonstrate that the polar cells act as an organizer that patterns surrounding follicle cells and establishes the anteroposterior axis of the oocyte. The origin of asymmetry during Drosophila development can thus be traced back to the specification of the polar cells during early oogenesis.

  16. Physical processes in polar stratospheric ice clouds

    NASA Technical Reports Server (NTRS)

    Toon, Owen B.; Ferry, G.; Turco, R. P.; Jordan, J.; Goodman, J.

    1989-01-01

    The formulation and evolution of polar stratospheric ice clouds are simulated using a one-dimensional model of cloud microphysics. It is found that the optical thickness and particle size of ice clouds depend on the cooling rate of the air in which the cloud formed. It is necessary that there be an energy barrier to ice nucleation upon the preexisting aerosols in order to account for the cooling rate dependence of the cloud properties.

  17. DLG5 in cell polarity maintenance and cancer development.

    PubMed

    Liu, Jie; Li, Juan; Ren, Yu; Liu, Peijun

    2014-01-01

    Failure in establishment and maintenance of epithelial cell polarity contributes to tumorigenesis. Loss of expression and function of cell polarity proteins is directly related to epithelial cell polarity maintenance. The polarity protein discs large homolog 5 (DLG5) belongs to a family of molecular scaffolding proteins called Membrane Associated Guanylate Kinases (MAGUKs). As the other family members, DLG5 contains the multi-PDZ, SH3 and GUK domains. DLG5 has evolved in the same manner as DLG1 and ZO1, two well-studied MAGUKs proteins. Just like DLG1 and ZO1, DLG5 plays a role in cell migration, cell adhesion, precursor cell division, cell proliferation, epithelial cell polarity maintenance, and transmission of extracellular signals to the membrane and cytoskeleton. Since the roles of DLG5 in inflammatory bowel disease (IBD) and Crohn's disease (CD) have been reviewed, here, our review focuses on the roles of DLG5 in epithelial cell polarity maintenance and cancer development.

  18. fringe and Notch specify polar cell fate during Drosophila oogenesis.

    PubMed

    Grammont, M; Irvine, K D

    2001-06-01

    fringe encodes a glycosyltransferase that modulates the ability of the Notch receptor to be activated by its ligands. We describe studies of fringe function during early stages of Drosophila oogenesis. Animals mutant for hypomorphic alleles of fringe contain follicles with an incorrect number of germline cells, which are separated by abnormally long and disorganized stalks. Analysis of clones of somatic cells mutant for a null allele of fringe localizes the requirement for fringe in follicle formation to the polar cells, and demonstrates that fringe is required for polar cell fate. Clones of cells mutant for Notch also lack polar cells and the requirement for Notch in follicle formation appears to map to the polar cells. Ectopic expression of fringe or of an activated form of Notch can generate an extra polar cell. Our results indicate that fringe plays a key role in positioning Notch activation during early oogenesis, and establish a function for the polar cells in separating germline cysts into individual follicles.

  19. Multifunctional aerial display through use of polarization-processing display

    NASA Astrophysics Data System (ADS)

    Uchida, Keitaro; Ito, Shusei; Yamamoto, Hirotsugu

    2017-02-01

    We have realized a multifunctional aerial display. An aerial image of a polarization-processing display is formed through aerial imaging by retro-reflection. By changing the polarization modulation patterns, we can switch between a three-layered display and a secure display.

  20. Auxin regulation of cell polarity in plants.

    PubMed

    Pan, Xue; Chen, Jisheng; Yang, Zhenbiao

    2015-12-01

    Auxin is well known to control pattern formation and directional growth at the organ/tissue levels via the nuclear TIR1/AFB receptor-mediated transcriptional responses. Recent studies have expanded the arena of auxin actions as a trigger or key regulator of cell polarization and morphogenesis. These actions require non-transcriptional responses such as changes in the cytoskeleton and vesicular trafficking, which are commonly regulated by ROP/Rac GTPase-dependent pathways. These findings beg for the question about the nature of auxin receptors that regulate these responses and renew the interest in ABP1 as a cell surface auxin receptor, including the work showing auxin-binding protein 1 (ABP1) interacts with the extracellular domain of the transmembrane kinase (TMK) receptor-like kinases in an auxin-dependent manner, as well as the debate on this auxin binding protein discovered about 40 years ago. This review highlights recent work on the non-transcriptional auxin signaling mechanisms underscoring cell polarity and shape formation in plants.

  1. Planar Cell Polarity Signaling in the Drosophila Eye

    PubMed Central

    Jenny, Andreas

    2017-01-01

    Planar cell polarity (PCP) signaling regulates the establishment of polarity within the plane of an epithelium and allows cells to obtain directional information. Its results are as diverse as the determination of cell fates, the generation of asymmetric but highly aligned structures (e.g., stereocilia in the human ear or hairs on a fly wing), or the directional migration of cells during convergent extension during vertebrate gastrulation. Aberrant PCP establishment can lead to human birth defects or kidney disease. PCP signaling is governed by the noncanonical Wnt or Fz/PCP pathway. Traditionally, PCP establishment has been best studied in Drosophila, mainly due to the versatility of the fly as a genetic model system. In Drosophila, PCP is essential for the orientation of wing and abdominal hairs, the orientation of the division axis of sensory organ precursors, and the polarization of ommatidia in the eye, the latter requiring a highly coordinated movement of groups of photoreceptor cells during the process of ommatidial rotation. Here, I review our current understanding of PCP signaling in the Drosophila eye and allude to parallels in vertebrates. PMID:20959167

  2. Planar cell polarity signaling in the Drosophila eye.

    PubMed

    Jenny, Andreas

    2010-01-01

    Planar cell polarity (PCP) signaling regulates the establishment of polarity within the plane of an epithelium and allows cells to obtain directional information. Its results are as diverse as the determination of cell fates, the generation of asymmetric but highly aligned structures (e.g., stereocilia in the human ear or hairs on a fly wing), or the directional migration of cells during convergent extension during vertebrate gastrulation. Aberrant PCP establishment can lead to human birth defects or kidney disease. PCP signaling is governed by the noncanonical Wnt or Fz/PCP pathway. Traditionally, PCP establishment has been best studied in Drosophila, mainly due to the versatility of the fly as a genetic model system. In Drosophila, PCP is essential for the orientation of wing and abdominal hairs, the orientation of the division axis of sensory organ precursors, and the polarization of ommatidia in the eye, the latter requiring a highly coordinated movement of groups of photoreceptor cells during the process of ommatidial rotation. Here, I review our current understanding of PCP signaling in the Drosophila eye and allude to parallels in vertebrates. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells

    PubMed Central

    Łangowski, Łukasz; Wabnik, Krzysztof; Li, Hongjiang; Vanneste, Steffen; Naramoto, Satoshi; Tanaka, Hirokazu; Friml, Jiří

    2016-01-01

    The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells. PMID:27462465

  4. Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells.

    PubMed

    Łangowski, Łukasz; Wabnik, Krzysztof; Li, Hongjiang; Vanneste, Steffen; Naramoto, Satoshi; Tanaka, Hirokazu; Friml, Jiří

    2016-01-01

    The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells.

  5. Focusing on the focus: what else beyond the master switches for polar cell growth?

    PubMed

    Qin, Yuan; Dong, Juan

    2015-04-01

    Cell polarity, often associated with polarized cell expansion/growth in plants, describes the uneven distribution of cellular components, such as proteins, nucleic acids, signaling molecules, vesicles, cytoskeletal elements, and organelles, which may ultimately modulate cell shape, structure, and function. Pollen tubes and root hairs are model cell systems for studying the molecular mechanisms underlying sustained tip growth. The formation of intercalated epidermal pavement cells requires excitatory and inhibitory pathways to coordinate cell expansion within single cells and between cells in contact. Strictly controlled cell expansion is linked to asymmetric cell division in zygotes and stomatal lineages, which require integrated processes of pre-mitotic cellular polarization and division asymmetry. While small GTPase ROPs are recognized as fundamental signaling switches for cell polarity in various cellular and developmental processes in plants, the broader molecular machinery underpinning polarity establishment required for asymmetric division remains largely unknown. Here, we review the widely used ROP signaling pathways in cell polar growth and the recently discovered feedback loops with auxin signaling and PIN effluxers. We discuss the conserved phosphorylation and phospholipid signaling mechanisms for regulating uneven distribution of proteins, as well as the potential roles of novel proteins and MAPKs in the polarity establishment related to asymmetric cell division in plants.

  6. Measuring receptor recycling in polarized MDCK cells.

    PubMed

    Gallo, Luciana; Apodaca, Gerard

    2015-01-01

    Recycling of proteins such as channels, pumps, and receptors is critical for epithelial cell function. In this chapter we present a method to measure receptor recycling in polarized Madin-Darby canine kidney cells using an iodinated ligand. We describe a technique to iodinate transferrin (Tf), we discuss how (125)I-Tf can be used to label a cohort of endocytosed Tf receptor, and then we provide methods to measure the rate of recycling of the (125)I-Tf-receptor complex. We also show how this approach, which is easily adaptable to other proteins, can be used to simultaneously measure the normally small amount of (125)I-Tf transcytosis and degradation.

  7. Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

    PubMed Central

    Eaton, Suzanne; Martin-Belmonte, Fernando

    2014-01-01

    The establishment and maintenance of polarized plasma membrane domains is essential for cellular function and proper development of organisms. Epithelial cells polarize along two fundamental axes, the apicobasal and the planar, both depending on finely regulated protein trafficking mechanisms. Newly synthesized proteins destined for either surface domain are processed along the biosynthetic pathway and segregated into distinct subsets of transport carriers emanating from the trans-Golgi network or endosomes. This exocytic trafficking has been identified as essential for proper epithelial polarization. Accumulating evidence now reveals that endocytosis and endocytic recycling play an equally important role in epithelial polarization and the appropriate localization of key polarity proteins. Here, we review recent work in metazoan systems illuminating the connections between endocytosis, postendocytic trafficking, and cell polarity, both apicobasal and planar, in the formation of differentiated epithelial cells, and how these processes regulate tissue dynamics. PMID:25125399

  8. Gpr125 modulates Dishevelled distribution and planar cell polarity signaling.

    PubMed

    Li, Xin; Roszko, Isabelle; Sepich, Diane S; Ni, Mingwei; Hamm, Heidi E; Marlow, Florence L; Solnica-Krezel, Lilianna

    2013-07-01

    During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly. Here, we have identified Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of the Wnt/PCP signaling system. Excess Gpr125 impaired C&E movements and the underlying cell and molecular polarities. Reduced Gpr125 function exacerbated the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/PCP signaling. At the molecular level, Gpr125 recruited Dishevelled to the cell membrane, a prerequisite for Wnt/PCP activation. Moreover, Gpr125 and Dvl mutually clustered one another to form discrete membrane subdomains, and the Gpr125 intracellular domain directly interacted with Dvl in pull-down assays. Intriguingly, Dvl and Gpr125 were able to recruit a subset of PCP components into membrane subdomains, suggesting that Gpr125 may modulate the composition of Wnt/PCP membrane complexes. Our study reveals a role for Gpr125 in PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling.

  9. Gpr125 modulates Dishevelled distribution and planar cell polarity signaling

    PubMed Central

    Li, Xin; Roszko, Isabelle; Sepich, Diane S.; Ni, Mingwei; Hamm, Heidi E.; Marlow, Florence L.; Solnica-Krezel, Lilianna

    2013-01-01

    During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly. Here, we have identified Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of the Wnt/PCP signaling system. Excess Gpr125 impaired C&E movements and the underlying cell and molecular polarities. Reduced Gpr125 function exacerbated the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/PCP signaling. At the molecular level, Gpr125 recruited Dishevelled to the cell membrane, a prerequisite for Wnt/PCP activation. Moreover, Gpr125 and Dvl mutually clustered one another to form discrete membrane subdomains, and the Gpr125 intracellular domain directly interacted with Dvl in pull-down assays. Intriguingly, Dvl and Gpr125 were able to recruit a subset of PCP components into membrane subdomains, suggesting that Gpr125 may modulate the composition of Wnt/PCP membrane complexes. Our study reveals a role for Gpr125 in PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling. PMID:23821037

  10. Mapping cellular processes in the mesenchyme during palatal development in the absence of Tbx1 reveals complex proliferation changes and perturbed cell packing and polarity.

    PubMed

    Brock, Lara J; Economou, Andrew D; Cobourne, Martyn T; Green, Jeremy B A

    2016-03-01

    The 22q11 deletion syndromes represent a spectrum of overlapping conditions including cardiac defects and craniofacial malformations. Amongst the craniofacial anomalies that are seen, cleft of the secondary palate is a common feature. Haploinsufficiency of TBX1 is believed to be a major contributor toward many of the developmental structural anomalies that occur in these syndromes, and targeted deletion of Tbx1 in the mouse reproduces many of these malformations, including cleft palate. However, the cellular basis of this defect is only poorly understood. Here, palatal development in the absence of Tbx1 has been analysed, focusing on cellular properties within the whole mesenchymal volume of the palatal shelves. Novel image analyses and data presentation tools were applied to quantify cell proliferation rates, including regions of elevated as well as reduced proliferation, and cell packing in the mesenchyme. Also, cell orientations (nucleus-Golgi axis) were mapped as a potential marker of directional cell movement. Proliferation differed only subtly between wild-type and mutant until embryonic day (E)15.5 when proliferation in the mutant was significantly lower. Tbx1(-/-) palatal shelves had slightly different cell packing than wild-type, somewhat lower before elevation and higher at E15.5 when the wild-type palate has elevated and fused. Cell orientation is biased towards the shelf distal edge in the mid-palate of wild-type embryos but is essentially random in the Tbx1(-/-) mutant shelves, suggesting that polarised processes such as directed cell rearrangement might be causal for the cleft phenotype. The implications of these findings in the context of further understanding Tbx1 function during palatogenesis and of these methods for the more general analysis of genotype-phenotype functional relationships are discussed.

  11. A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization.

    PubMed

    Ozbudak, Ertugrul M; Becskei, Attila; van Oudenaarden, Alexander

    2005-10-01

    Cellular polarization is often a response to distinct extracellular or intracellular cues, such as nutrient gradients or cortical landmarks. However, in the absence of such cues, some cells can still select a polarization axis at random. Positive feedback loops promoting localized activation of the GTPase Cdc42p are central to this process in budding yeast. Here, we explore spontaneous polarization during bud site selection in mutant yeast cells that lack functional landmarks. We find that these cells do not select a single random polarization axis, but continuously change this axis during the G1 phase of the cell cycle. This is reflected in traveling waves of activated Cdc42p which randomly explore the cell periphery. Our integrated computational and in vivo analyses of these waves reveal a negative feedback loop that competes with the aforementioned positive feedback loops to regulate Cdc42p activity and confer dynamic responsiveness on the robust initiation of cell polarization.

  12. Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.

    PubMed

    Mah, In Kyoung; Soloff, Rachel; Izuhara, Audrey K; Lakeland, Daniel L; Wang, Charles; Mariani, Francesca V

    2016-08-01

    Polarized epithelia define boundaries, spaces, and cavities within organisms. Cavitation, a process by which multicellular hollow balls or tubes are produced, is typically associated with the formation of organized epithelia. In order for these epithelial layers to form, cells must ultimately establish a distinct apical-basal polarity. Atypical PKCs have been proposed to be required for apical-basal polarity in diverse species. Here we show that while cells null for the Prkci isozyme exhibit some polarity characteristics, they fail to properly segregate apical-basal proteins, form a coordinated ectodermal epithelium, or participate in normal cavitation. A failure to cavitate could be due to an overgrowth of interior cells or to an inability of interior cells to die. Null cells however, do not have a marked change in proliferation rate and are still capable of undergoing cell death, suggesting that alterations in these processes are not the predominant cause of the failed cavitation. Overexpression of BMP4 or EZRIN can partially rescue the phenotype possibly by promoting cell death, polarity, and differentiation. However, neither is sufficient to provide the required cues to generate a polarized epithelium and fully rescue cavitation. Interestingly, when wildtype and Prkci(-/-) ES cells are mixed together, a polarized ectodermal epithelium forms and cavitation is rescued, likely due to the ability of wildtype cells to produce non-autonomous polarity cues. We conclude that Prkci is not required for cells to respond to these cues, though it is required to produce them. Together these findings indicate that environmental cues can facilitate the formation of polarized epithelia and that cavitation requires the proper coordination of multiple basic cellular processes including proliferation, differentiation, cell death, and apical-basal polarization.

  13. Prion infection of epithelial Rov cells is a polarized event.

    PubMed

    Paquet, Sophie; Sabuncu, Elifsu; Delaunay, Jean-Louis; Laude, Hubert; Vilette, Didier

    2004-07-01

    During prion infections, the cellular glycosylphosphatidylinositol-anchored glycoprotein PrP is converted into a conformational isoform. This abnormal conformer is thought to recruit and convert the normal cellular PrP into a likeness of itself and is proposed to be the infectious agent. We investigated the distribution of the PrP protein on the surface of Rov cells, an epithelial cell line highly permissive to prion multiplication, and we found that PrP is primarily expressed on the apical side. We further show that prion transmission to Rov cells is much more efficient if infectivity contacts the apical side, indicating that the apical and basolateral sides of Rov cells are not equally competent for prion infection and adding prions to the list of the conventional infectious agents (viruses and bacteria) that infect epithelial cells in a polarized manner. These data raise the possibility that apically expressed PrP may be involved in this polarized process of infection. This would add further support for a crucial role of PrP at the cell surface in prion infection of target cells.

  14. Prion Infection of Epithelial Rov Cells Is a Polarized Event

    PubMed Central

    Paquet, Sophie; Sabuncu, Elifsu; Delaunay, Jean-Louis; Laude, Hubert; Vilette, Didier

    2004-01-01

    During prion infections, the cellular glycosylphosphatidylinositol-anchored glycoprotein PrP is converted into a conformational isoform. This abnormal conformer is thought to recruit and convert the normal cellular PrP into a likeness of itself and is proposed to be the infectious agent. We investigated the distribution of the PrP protein on the surface of Rov cells, an epithelial cell line highly permissive to prion multiplication, and we found that PrP is primarily expressed on the apical side. We further show that prion transmission to Rov cells is much more efficient if infectivity contacts the apical side, indicating that the apical and basolateral sides of Rov cells are not equally competent for prion infection and adding prions to the list of the conventional infectious agents (viruses and bacteria) that infect epithelial cells in a polarized manner. These data raise the possibility that apically expressed PrP may be involved in this polarized process of infection. This would add further support for a crucial role of PrP at the cell surface in prion infection of target cells. PMID:15194791

  15. Superresolution microscopy reveals a dynamic picture of cell polarity maintenance during directional growth.

    PubMed

    Ishitsuka, Yuji; Savage, Natasha; Li, Yiming; Bergs, Anna; Grün, Nathalie; Kohler, Daria; Donnelly, Rebecca; Nienhaus, G Ulrich; Fischer, Reinhard; Takeshita, Norio

    2015-11-01

    Polar (directional) cell growth, a key cellular mechanism shared among a wide range of species, relies on targeted insertion of new material at specific locations of the plasma membrane. How these cell polarity sites are stably maintained during massive membrane insertion has remained elusive. Conventional live-cell optical microscopy fails to visualize polarity site formation in the crowded cell membrane environment because of its limited resolution. We have used advanced live-cell imaging techniques to directly observe the localization, assembly, and disassembly processes of cell polarity sites with high spatiotemporal resolution in a rapidly growing filamentous fungus, Aspergillus nidulans. We show that the membrane-associated polarity site marker TeaR is transported on microtubules along with secretory vesicles and forms a protein cluster at that point of the apical membrane where the plus end of the microtubule touches. There, a small patch of membrane is added through exocytosis, and the TeaR cluster gets quickly dispersed over the membrane. There is an incessant disassembly and reassembly of polarity sites at the growth zone, and each new polarity site locus is slightly offset from preceding ones. On the basis of our imaging results and computational modeling, we propose a transient polarity model that explains how cell polarity is stably maintained during highly active directional growth.

  16. Lethal (2) giant larvae: an indispensable regulator of cell polarity and cancer development.

    PubMed

    Cao, Fang; Miao, Yi; Xu, Kedong; Liu, Peijun

    2015-01-01

    Cell polarity is one of the most basic properties of all normal cells and is essential for regulating numerous biological processes. Loss of polarity is considered a hallmark for cancer. Multiple polarity proteins are implicated in maintenance of cell polarity. Lethal (2) giant larvae (Lgl) is one of polarity proteins that plays an important role in regulating cell polarity, asymmetric division as well as tumorigenesis. Lgl proteins in different species have similar structures and conserved functions. Lgl acts as an indispensable regulator of cell biological function, including cell polarity and asymmetric division, through interplaying with other polarity proteins, regulating exocytosis, mediating cytoskeleton and being involved in signaling pathways. Furthermore, Lgl plays a role of a tumor suppressor, and the aberrant expression of Hugl, a human homologue of Lgl, contributes to multiple cancers. However, the exact functions of Lgl and the underlying mechanisms remain enigmatic. In this review, we will give an overview of the Lgl functions in cell polarity and cancer development, discuss the potential mechanisms underlying these functions, and raise our conclusion of previous studies and points of view about the future studies.

  17. Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42.

    PubMed Central

    Stowers, L; Yelon, D; Berg, L J; Chant, J

    1995-01-01

    The mechanisms by which cells rapidly polarize in the direction of external signals are not understood. Helper T cells, when contacted by an antigen-presenting cell, polarize their cytoskeletons toward the antigen-presenting cell within minutes. Here we show that, in T cells, the mammalian Ras-related GTPase CDC42 (the homologue of yeast CDC42, a protein involved in budding polarity) can regulate the polarization of both actin and microtubules toward antigen-presenting cells but is not involved in other T-cell signaling processes such as those which culminate in interleukin 2 production. Although T-cell polarization appears dispensable for signaling leading to interleukin 2 production, polarization may direct lymphokine secretion towards the correct antigen-presenting cell in a crowded cellular environment. Inhibitor experiments suggest that phosphatidylinositol 3-kinase is required for cytoskeletal polarization but that calcineurin activity, known to be important for other aspects of signaling, is not. Apparent conservation of CDC42 function between yeast and T cells suggests that this GTPase is a general regulator of cytoskeletal polarity in many cell types. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7761442

  18. Atomic processes in strong bichromatic elliptically polarized laser fields

    SciTech Connect

    Odžak, S. Hasović, E.; Gazibegović-Busuladžić, A.; Čerkić, A. Fetić, B.; Kramo, A.; Busuladžić, M.; Milošević, D. B.

    2016-03-25

    Nonlinear quantum-mechanical phenomena in strong laser fields, such as high-order harmonic generation (HHG) and above-threshold ionization (ATI) are significantly modified if the applied laser field is bichromatic and/or elliptically polarized. Numerical results obtained within the strong-field approximation are presented for two special cases. We show results for HHG by plasma ablation in a bichromatic linearly polarized laser field. We also consider the ATI process in bicircular field which consists of two coplanar counter-rotating circularly polarized fields.

  19. A process for low cost wire grid polarizers

    NASA Astrophysics Data System (ADS)

    Watts, M. P. C.; Little, M.; Egan, E.; Hochbaum, A.; Johns, C.; Stephansen, S.

    2013-03-01

    Oblique angle metal deposition has been combined with high aspect ratio imprinted structures to create wire grid polarizers (WGP's) for use as polarization recyclers in liquid crystal displays. The process of oblique deposition was simulated to determine optimal feature profile and deposition geometry. The optical results for the oblique deposition WGP show contrast comparable to a conventionally etched WGP. The next steps to the fabrication of meter sized WGP are proposed.

  20. Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation

    PubMed Central

    Vladar, Eszter K.; Nayak, Jayakar V.; Milla, Carlos E.; Axelrod, Jeffrey D.

    2016-01-01

    Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease. PMID:27570836

  1. Damped propagation of cell polarization explains distinct PCP phenotypes of epithelial patterning

    PubMed Central

    Zhu, Hao; Owen, Markus R.

    2013-01-01

    During epithelial patterning in metazoans cells are polarized in the plane of a tissue, a process referred to as planar cell polarity (PCP). Interactions between a few molecules produce distinct phenotypes in diverse tissues in animals from flies to humans and make PCP tightly associated with tissue and organ growth control. An interesting question is whether these phenotypes share common traits. Previous computational models revealed how PCP signalling determines cell polarization in some specific contexts. We have developed a computational model, examined PCP signalling in varied molecular contexts, and revealed how details of molecular interactions and differences in molecular contexts affect the direction, speed, and propagation of cell polarization. The main finding is that damped propagation of cell polarization can generate rich variances in phenotypes of domineering non-autonomy and error correction in different contexts. These results impressively demonstrate how simple molecular interactions cause distinct, yet inherently analogous, developmental patterning. PMID:23995897

  2. Phosphatidylserine is polarized and required for proper Cdc42 localization and for development of cell polarity.

    PubMed

    Fairn, Gregory D; Hermansson, Martin; Somerharju, Pentti; Grinstein, Sergio

    2011-10-02

    Polarity is key to the function of eukaryotic cells. On the establishment of a polarity axis, cells can vectorially target secretion, generating an asymmetric distribution of plasma membrane proteins. From Saccharomyces cerevisiae to mammals, the small GTPase Cdc42 is a pivotal regulator of polarity. We used a fluorescent probe to visualize the distribution of phosphatidylserine in live S. cerevisiae. Remarkably, phosphatidylserine was polarized in the plasma membrane, accumulating in bud necks, the bud cortex and the tips of mating projections. Polarization required vectorial delivery of phosphatidylserine-containing secretory vesicles, and phosphatidylserine was largely excluded from endocytic vesicles, contributing to its polarized retention. Mutants lacking phosphatidylserine synthase had impaired polarization of the Cdc42 complex, leading to a delay in bud emergence, and defective mating. The addition of lysophosphatidylserine resulted in resynthesis and polarization of phosphatidylserine, as well as repolarization of Cdc42. The results indicate that phosphatidylserine--and presumably its polarization--are required for optimal Cdc42 targeting and activation during cell division and mating.

  3. The reorientation of cell nucleus promotes the establishment of front-rear polarity in migrating fibroblasts.

    PubMed

    Maninová, Miloslava; Klímová, Zuzana; Parsons, J Thomas; Weber, Michael J; Iwanicki, Marcin P; Vomastek, Tomáš

    2013-06-12

    The establishment of cell polarity is an essential step in the process of cell migration. This process requires precise spatiotemporal coordination of signaling pathways that in most cells create the typical asymmetrical profile of a polarized cell with nucleus located at the cell rear and the microtubule organizing center (MTOC) positioned between the nucleus and the leading edge. During cell polarization, nucleus rearward positioning promotes correct microtubule organizing center localization and thus the establishment of front-rear polarity and directional migration. We found that cell polarization and directional migration require also the reorientation of the nucleus. Nuclear reorientation is manifested as temporally restricted nuclear rotation that aligns the nuclear axis with the axis of cell migration. We also found that nuclear reorientation requires physical connection between the nucleus and cytoskeleton mediated by the LINC (linker of nucleoskeleton and cytoskeleton) complex. Nuclear reorientation is controlled by coordinated activity of lysophosphatidic acid (LPA)-mediated activation of GTPase Rho and the activation of integrin, FAK (focal adhesion kinase), Src, and p190RhoGAP signaling pathway. Integrin signaling is spatially induced at the leading edge as FAK and p190RhoGAP are predominantly activated or localized at this location. We suggest that integrin activation within lamellipodia defines cell front, and subsequent FAK, Src, and p190RhoGAP signaling represents the polarity signal that induces reorientation of the nucleus and thus promotes the establishment of front-rear polarity.

  4. Planar Cell Polarity Signaling: From Fly Development to Human Disease

    PubMed Central

    Simons, Matias; Mlodzik, Marek

    2009-01-01

    Most, if not all, cell types and tissues display several aspects of polarization. In addition to the ubiquitous epithelial cell polarity along the apical-basolateral axis, many epithelial tissues and organs are also polarized within the plane of the epithelium. This is generally referred to as planar cell polarity (PCP; or historically, tissue polarity). Genetic screens in Drosophila pioneered the discovery of core PCP factors, and subsequent work in vertebrates has established that the respective pathways are evolutionarily conserved. PCP is not restricted only to epithelial tissues but is also found in mesenchymal cells, where it can regulate cell migration and cell intercalation. Moreover, particularly in vertebrates, the conserved core PCP signaling factors have recently been found to be associated with the orientation or formation of cilia. This review discusses new developments in the molecular understanding of PCP establishment in Drosophila and vertebrates; these developments are integrated with new evidence that links PCP signaling to human disease. PMID:18710302

  5. Critical assessment of fluorescence polarization measurements with a FACS IV cell sorter

    NASA Astrophysics Data System (ADS)

    Muller, Claude P.; Krabichler, Gert

    1988-09-01

    The usefulness and limitations of the Becton-Dickinson fluorescence-activated cell sorter FACS IV for fluorescence polarization measurements were examined. A set of tests to determine the characteristics of the detection geometry, the optical properties of the beam splitter, and the capability to process fluorescence polarization data is presented. Recommendations are provided for correcting instrumental deficiencies.

  6. Cytokinesis and the establishment of early embryonic cell polarity.

    PubMed

    Burgess, David R

    2008-06-01

    Cleavage divisions in many animals form a blastula made up of a simple polarized epithelium. This simple embryonic epithelium possesses an apical surface covered with microvilli and primary cilia separated from the basolateral surfaces by cell-cell junctions. The apical membrane proteins and lipids differ from those of the basolateral on these embryonic epithelial cells, as is found in adult epithelial cells. Formation of cell polarity in embryos at fertilization, including those from both protostomes and deuterostomes, uses the same molecules and signalling machinery as do polarizing epithelial cells that polarize upon cell-cell contact. In addition, the actin-myosin cytoskeleton plays an integral role in establishment and maintenance of this early cell polarity. However, early cleaving blastomeres from higher organisms including echinoderms and vertebrates have not been considered to exhibit cell polarity until formation of junctions at the third through to the fifth cleavage divisions. The role of new membrane addition into the late cleavage furrow during the early rounds of cytokinesis may play a key role in the early establishment of cell polarity in all animal embryos.

  7. Polarization-based non-staining cell detection.

    PubMed

    Zhang, M; Ihida-Stansbury, K; Van der Spiegel, J; Engheta, N

    2012-11-05

    Polarization is an important characteristic of electromagnetic waves, which can not be detected by either the human visual system or traditional image sensors. Motivated by various animal species with polarization vision as well as by the prospect of improving the image quality of the imaging systems, we are exploring the potential of polarization for microscope imaging. The most powerful techniques for molecule monitoring requires complex preprocessing for labeling the sample with different dyes. In this paper, we propose a cell detection method using polarization imaging without any need for staining target cell samples with any chemical dye. The motivation for this work is to develop an optical imaging technique that is simple and that can be used on live cells. The polarization sensitivity of cell samples is studied in this paper. A definition for the quantity called "polarization deviation" is proposed in order to identify clearer the difference between target cells and the background. Based on the polarization deviation detection method, a three-parameter polarization imaging method is employed to further simplify the image capture procedure for the proposed label-free cell detection. A color imaging methodology based on the well-known color space is utilized in order to represent the captured polarization information using computer graphics.

  8. Measurement of dynamic variations of polarized light in processed meat due to aging

    NASA Astrophysics Data System (ADS)

    Abubaker, Hamed M.; Tománek, Pavel; Grmela, Lubomír

    2011-05-01

    The propagation of laser light in biological tissues is of growing importance in many medical and food applications. This problem is seriously studied in live science. The biological tissues consist of cells which dimensions are bigger than wavelength of visible light and display large compositional variations, inhomogeneities, and anisotropic structures. Therefore a Mie scattering of transmitted or backscattered light occurs and different polarization states arise. The changes of polarization state due to the multiple scattering of light in the biological cellular tissues also allow measure the freshness of processed victuals. The transmitted and backscattered laser light exhibits multiple scattering on the thin slice of sample. The phenomenon is different if the cellular tissues are living or dead. In the case of meat, there are temporal and dynamic changes not only as a result of chemical process, but also geometric deformations due to the water evaporation from intracellular and extracellular sites. The polarization measurement shows the changes in polarization orientation due to the muscle orientation and meat aging. Two types of measurements were provided: a) Measurement of polarized light reflected and twice transmitted forward and backward through the biological tissue samples - meat slice attached on sample holder mirror. b) Measurement of polarized light transmitted through the biological tissue sample. The relationship between polarization changes and meat freshness, and a dynamic temporal behavior of polarization states in the aged meat is reported.

  9. Insights into the mechanism for dictating polarity in migrating T-cells.

    PubMed

    Niggli, Verena

    2014-01-01

    This review is focused on mechanisms of chemokine-induced polarization of T-lymphocytes. Polarization involves, starting from spherical cells, formation of a morphologically and functionally different rear (uropod) and front (leading edge). This polarization is required for efficient random and directed T-cell migration. The addressed topics concern the specific location of cell organelles and of receptors, signaling molecules, and cytoskeletal proteins in chemokine-stimulated polarized T-cells. In chemokine-stimulated, polarized T-cells, specific proteins, signaling molecules and organelles show enrichment either in the rear, the midzone, or the front; different from the random location in spherical resting cells. Possible mechanisms involved in this asymmetric location will be discussed. A major topic is also the functional role of proteins and cell organelles in T-cell polarization and migration. Specifically, the roles of adhesion and chemokine receptors, cytoskeletal proteins, signaling molecules, scaffolding proteins, and membrane microdomains in these processes will be discussed. The polarity which is established during contact formation of T-cells with antigen-presenting cells is not discussed in detail.

  10. Positioning of polarity formation by extracellular signaling during asymmetric cell division.

    PubMed

    Seirin Lee, Sungrim

    2016-07-07

    Anterior-posterior (AP) polarity formation of cell membrane proteins plays a crucial role in determining cell asymmetry, which ultimately generates cell diversity. In Caenorhabditis elegans, a single fertilized egg cell (P0), its daughter cell (P1), and the germline precursors (P2 and P3 cells) form two exclusive domains of different PAR proteins on the membrane along the anterior-posterior axis. However, the phenomenon of polarity reversal has been observed in which the axis of asymmetric cell division of the P2 and P3 cells is formed in an opposite manner to that of the P0 and P1 cells. The extracellular signal MES-1/SRC-1 has been shown to induce polarity reversal, but the detailed mechanism remains elusive. Here, using a mathematical model, I explore the mechanism by which MES-1/SRC-1 signaling can induce polarity reversal and ultimately affect the process of polarity formation. I show that a positive correlation between SRC-1 and the on-rate of PAR-2 is the essential mechanism underlying polarity reversal, providing a mathematical basis for the orientation of cell polarity patterns.

  11. Getting to the root of plant iron uptake and cell-cell transport: Polarity matters!

    PubMed

    Dubeaux, Guillaume; Zelazny, Enric; Vert, Grégory

    2015-01-01

    Plasma membrane proteins play pivotal roles in mediating responses to endogenous and environmental cues. Regulation of membrane protein levels and establishment of polarity are fundamental for many cellular processes. In plants, IRON-REGULATED TRANSPORTER 1 (IRT1) is the major root iron transporter but is also responsible for the absorption of other divalent metals such as manganese, zinc and cobalt. We recently uncovered that IRT1 is polarly localized to the outer plasma membrane domain of plant root epidermal cells upon depletion of its secondary metal substrates. The endosome-recruited FYVE1 protein interacts with IRT1 in the endocytic pathway and plays a crucial role in the establishment of IRT1 polarity, likely through its recycling to the cell surface. Our work sheds light on the mechanisms of radial transport of nutrients across the different cell types of plant roots toward the vascular tissues and raises interesting parallel with iron transport in mammals.

  12. Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development

    PubMed Central

    Sokol, Sergei Y.

    2015-01-01

    Wnt signaling pathways act at multiple locations and developmental stages to specify cell fate and polarity in vertebrate embryos. A long-standing question is how the same molecular machinery can be reused to produce different outcomes. The canonical Wnt/β-catenin branch modulates target gene transcription to specify cell fates along the dorsoventral and anteroposterior embryonic axes. By contrast, the Wnt/planar cell polarity (PCP) branch is responsible for cell polarization along main body axes, which coordinates morphogenetic cell behaviors during gastrulation and neurulation. Whereas both cell fate and cell polarity are modulated by spatially- and temporally-restricted Wnt activity, the downstream signaling mechanisms are very diverse. This review highlights recent progress in the understanding of Wnt-dependent molecular events leading to the establishment of PCP and linking it to early morphogenetic processes. PMID:25986055

  13. Clean thermal decomposition of tertiary-alkyl metal thiolates to metal sulfides: environmentally-benign, non-polar inks for solution-processed chalcopyrite solar cells

    NASA Astrophysics Data System (ADS)

    Heo, Jungwoo; Kim, Gi-Hwan; Jeong, Jaeki; Yoon, Yung Jin; Seo, Jung Hwa; Walker, Bright; Kim, Jin Young

    2016-11-01

    We report the preparation of Cu2S, In2S3, CuInS2 and Cu(In,Ga)S2 semiconducting films via the spin coating and annealing of soluble tertiary-alkyl thiolate complexes. The thiolate compounds are readily prepared via the reaction of metal bases and tertiary-alkyl thiols. The thiolate complexes are soluble in common organic solvents and can be solution processed by spin coating to yield thin films. Upon thermal annealing in the range of 200–400 °C, the tertiary-alkyl thiolates decompose cleanly to yield volatile dialkyl sulfides and metal sulfide films which are free of organic residue. Analysis of the reaction byproducts strongly suggests that the decomposition proceeds via an SN1 mechanism. The composition of the films can be controlled by adjusting the amount of each metal thiolate used in the precursor solution yielding bandgaps in the range of 1.2 to 3.3 eV. The films form functioning p-n junctions when deposited in contact with CdS films prepared by the same method. Functioning solar cells are observed when such p-n junctions are prepared on transparent conducting substrates and finished by depositing electrodes with appropriate work functions. This method enables the fabrication of metal chalcogenide films on a large scale via a simple and chemically clear process.

  14. Clean thermal decomposition of tertiary-alkyl metal thiolates to metal sulfides: environmentally-benign, non-polar inks for solution-processed chalcopyrite solar cells

    PubMed Central

    Heo, Jungwoo; Kim, Gi-Hwan; Jeong, Jaeki; Yoon, Yung Jin; Seo, Jung Hwa; Walker, Bright; Kim, Jin Young

    2016-01-01

    We report the preparation of Cu2S, In2S3, CuInS2 and Cu(In,Ga)S2 semiconducting films via the spin coating and annealing of soluble tertiary-alkyl thiolate complexes. The thiolate compounds are readily prepared via the reaction of metal bases and tertiary-alkyl thiols. The thiolate complexes are soluble in common organic solvents and can be solution processed by spin coating to yield thin films. Upon thermal annealing in the range of 200–400 °C, the tertiary-alkyl thiolates decompose cleanly to yield volatile dialkyl sulfides and metal sulfide films which are free of organic residue. Analysis of the reaction byproducts strongly suggests that the decomposition proceeds via an SN1 mechanism. The composition of the films can be controlled by adjusting the amount of each metal thiolate used in the precursor solution yielding bandgaps in the range of 1.2 to 3.3 eV. The films form functioning p-n junctions when deposited in contact with CdS films prepared by the same method. Functioning solar cells are observed when such p-n junctions are prepared on transparent conducting substrates and finished by depositing electrodes with appropriate work functions. This method enables the fabrication of metal chalcogenide films on a large scale via a simple and chemically clear process. PMID:27827402

  15. Clean thermal decomposition of tertiary-alkyl metal thiolates to metal sulfides: environmentally-benign, non-polar inks for solution-processed chalcopyrite solar cells.

    PubMed

    Heo, Jungwoo; Kim, Gi-Hwan; Jeong, Jaeki; Yoon, Yung Jin; Seo, Jung Hwa; Walker, Bright; Kim, Jin Young

    2016-11-09

    We report the preparation of Cu2S, In2S3, CuInS2 and Cu(In,Ga)S2 semiconducting films via the spin coating and annealing of soluble tertiary-alkyl thiolate complexes. The thiolate compounds are readily prepared via the reaction of metal bases and tertiary-alkyl thiols. The thiolate complexes are soluble in common organic solvents and can be solution processed by spin coating to yield thin films. Upon thermal annealing in the range of 200-400 °C, the tertiary-alkyl thiolates decompose cleanly to yield volatile dialkyl sulfides and metal sulfide films which are free of organic residue. Analysis of the reaction byproducts strongly suggests that the decomposition proceeds via an SN1 mechanism. The composition of the films can be controlled by adjusting the amount of each metal thiolate used in the precursor solution yielding bandgaps in the range of 1.2 to 3.3 eV. The films form functioning p-n junctions when deposited in contact with CdS films prepared by the same method. Functioning solar cells are observed when such p-n junctions are prepared on transparent conducting substrates and finished by depositing electrodes with appropriate work functions. This method enables the fabrication of metal chalcogenide films on a large scale via a simple and chemically clear process.

  16. Self-organization and advective transport in the cell polarity formation for asymmetric cell division.

    PubMed

    Seirin Lee, Sungrim; Shibata, Tatsuo

    2015-10-07

    Anterior-Posterior (AP) polarity formation of cell membrane proteins plays a crucial role in determining cell asymmetry, which depends not only on the several genetic process but also biochemical and biophysical interactions. The mechanism of AP formation of Caenorhabditis elegans embryo is characterized into the three processes: (i) membrane association and dissociation of posterior and anterior proteins, (ii) diffusion into the membrane and cytosol, and (iii) active cortical and cytoplasmic flows induced by the contraction of the acto-myosin cortex. We explored the mechanism of symmetry breaking and AP polarity formation using self-recruitment model of posterior proteins. We found that the AP polarity pattern is established over wide range in the total mass of polarity proteins and the diffusion ratio in the cytosol to the membrane. We also showed that the advective transport in both membrane and cytosol during the establishment phase affects optimal time interval of establishment and positioning of the posterior domain, and plays a role to increase the robustness in the AP polarity formation by reducing the number of posterior domains for the sensitivity of initial conditions. We also demonstrated that a proper ratio of the total mass to cell size robustly regulate the length scale of the posterior domain.

  17. Proceedings of the Polar Processes on Mars Workshop

    NASA Astrophysics Data System (ADS)

    Haberle, Robert M.

    1988-12-01

    Included in this publication is a collection of abstracts from the NASA-sponsored workshop, Polar Processes on Mars, which was held at the Sunnyvale Hilton Hotel, Sunnyvale, California, on 12 to 13 May 1988. Support for the workshop came from NASA's Planetary Geology and Geophysics program managed by Dr. Jospeh Boyce. The workshop is one of a series identified by MECA (an acronym for Mars: Evolution of its Climate and Atmosphere) as being worthy of focused research, but one for which it was not possible to hold during the project's lifetime. Consequently, it was held after the project ended. The MECA project was part of the Mars Data Analysis program. The workshop consisted of four sessions: The Polar Caps, Dynamics/Atmospheric Processes, Polar Geology, and Future Measurements. To put things into perspective, each of the first three sessions began with a review. All sessions were scheduled to allow ample time for discussion. A brief review of each session is provided.

  18. Dusty plasma processes in Earth's polar summer mesosphere

    NASA Astrophysics Data System (ADS)

    Popel, S. I.; Dubinsky, A. Yu.; Dubinsky

    2013-08-01

    A self-consistent model for the description of dusty plasma structures, such as noctilucent clouds (NLC) and polar mesosphere summer echoes (PMSE), which are frequently grouped together under the common term polar mesospheric clouds, is presented. The model takes into account the processes of condensation of water vapor, ionization, recombination, action of solar radiation, sedimentation, dust particle growth, dust particle charging, electric fields, etc. Using the model, we explain the basic data of observations on the behavior of charged component in polar summer mesosphere. Furthermore, we show the influence of initial distributions of fine particles as well as that of the processes of condensation and water molecule absorption by fine particles on the formation of NLC and PMSE. We also illustrate the possibility of the formation of layered structure and sharp boundaries of NLC.

  19. Proceedings of the Polar Processes on Mars Workshop

    NASA Technical Reports Server (NTRS)

    Haberle, Robert M.

    1988-01-01

    Included in this publication is a collection of abstracts from the NASA-sponsored workshop, Polar Processes on Mars, which was held at the Sunnyvale Hilton Hotel, Sunnyvale, California, on 12 to 13 May 1988. Support for the workshop came from NASA's Planetary Geology and Geophysics program managed by Dr. Jospeh Boyce. The workshop is one of a series identified by MECA (an acronym for Mars: Evolution of its Climate and Atmosphere) as being worthy of focused research, but one for which it was not possible to hold during the project's lifetime. Consequently, it was held after the project ended. The MECA project was part of the Mars Data Analysis program. The workshop consisted of four sessions: The Polar Caps, Dynamics/Atmospheric Processes, Polar Geology, and Future Measurements. To put things into perspective, each of the first three sessions began with a review. All sessions were scheduled to allow ample time for discussion. A brief review of each session is provided.

  20. Electrical control of cell polarization in the fission yeast Schizosaccharomyces pombe.

    PubMed

    Minc, Nicolas; Chang, Fred

    2010-04-27

    Electric signals surround tissues and cells and have been proposed to participate in directing cell polarity in processes such as development, wound healing, and host invasion [1, 2]. The application of exogenous electric fields (EFs) can direct cell polarization in cell types ranging from bacteria and fungi to neurons and neutrophils [3-7]. The mechanisms by which EFs modulate cell polarity, however, remain poorly understood. Here we introduce the fission yeast Schizosaccharomyces pombe as a model organism to elucidate the mechanisms underlying this process. In these rod-shaped cells, an exogenous EF reorients cell growth in a direction orthogonal to the field, producing cells with a bent morphology. A candidate genetic screen identifies conserved factors involved in this process: an integral membrane proton ATPase pma1p that regulates intracellular pH, the small GTPase cdc42p, and the formin for3p that assembles actin cables. Interestingly, mutants in these genes still respond to the EF but orient in a different direction, toward the anode. In addition, EFs also cause electrophoretic movement of cell wall synthase complex proteins toward the anode. These data suggest molecular models for how the EF reorients cell polarization by modulating intracellular pH and steering cell polarity factors in multiple directions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Planar cell polarity: keeping hairs straight is not so simple.

    PubMed

    McNeill, Helen

    2010-02-01

    The fur on a cat's back, the scales on a fish, or the bristles on a fly are all beautifully organized, with a high degree of polarization in their surface organization. Great progress has been made in understanding how individual cell polarity is established, but our understanding of how cells coordinate their polarity in forming coherent tissues is still fragmentary. The organization of cells in the plane of the epithelium is known as planar cell polarity (PCP), and studies in the past decade have delineated a genetic pathway for the control of PCP. This review will first briefly review data from the Drosophila field, where PCP was first identified and genetically characterized, and then explore how vertebrate tissues become polarized during development.

  2. Pak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis.

    PubMed

    Felix, Martina; Chayengia, Mrinal; Ghosh, Ritabrata; Sharma, Aditi; Prasad, Mohit

    2015-11-01

    Group cell migration is a highly coordinated process that is involved in a number of physiological events such as morphogenesis, wound healing and tumor metastasis. Unlike single cells, collectively moving cells are physically attached to each other and retain some degree of apical-basal polarity during the migratory phase. Although much is known about direction sensing, how polarity is regulated in multicellular movement remains unclear. Here we report the role of the protein kinase Pak3 in maintaining apical-basal polarity in migrating border cell clusters during Drosophila oogenesis. Pak3 is enriched in border cells and downregulation of its function impedes border cell movement. Time-lapse imaging suggests that Pak3 affects protrusive behavior of the border cell cluster, specifically regulating the stability and directionality of protrusions. Pak3 functions downstream of guidance receptor signaling to regulate the level and distribution of F-actin in migrating border cells. We also provide evidence that Pak3 genetically interacts with the lateral polarity marker Scribble and that it regulates JNK signaling in the moving border cells. Since Pak3 depletion results in mislocalization of several apical-basal polarity markers and overexpression of Jra rescues the polarity of the Pak3-depleted cluster, we propose that Pak3 functions through JNK signaling to modulate apical-basal polarity of the migrating border cell cluster. We also observe loss of apical-basal polarity in Rac1-depleted border cell clusters, suggesting that guidance receptor signaling functions through Rac GTPase and Pak3 to regulate the overall polarity of the cluster and mediate efficient collective movement of the border cells to the oocyte boundary.

  3. Retracing the path of planar cell polarity.

    PubMed

    Schenkelaars, Quentin; Fierro-Constain, Laura; Renard, Emmanuelle; Borchiellini, Carole

    2016-04-02

    The Planar Cell Polarity pathway (PCP) has been described as the main feature involved in patterning cell orientation in bilaterian tissues. Recently, a similar phenomenon was revealed in cnidarians, in which the inhibition of this pathway results in the absence of cilia orientation in larvae, consequently proving the functional conservation of PCP signaling between Cnidaria and Bilateria. Nevertheless, despite the growing accumulation of databases concerning basal lineages of metazoans, very few information concerning the existence of PCP components have been gathered outside of Bilateria and Cnidaria. Thus, the origin of this module or its prevalence in early emerging metazoans has yet to be elucidated. The present study addresses this question by investigating the genomes and transcriptomes from all poriferan lineages in addition to Trichoplax (Placozoa) and Mnemiopsis (Ctenophora) genomes for the presence of the core components of this pathway. Our results confirm that several PCP components are metazoan innovations. In addition, we show that all members of the PCP pathway, including a bona fide Strabismus ortholog (Van gogh), are retrieved only in one sponge lineage (Homoscleromorpha) out of four. This highly suggests that the full PCP pathway dates back at least to the emergence of homoscleromorph sponges. Consequently, several secondary gene losses would have occurred in the three other poriferan lineages including Amphimedon queenslandica (Demospongiae). Several proteins were not retrieved either in placozoans or ctenophores leading us to discuss the difficulties to predict orthologous proteins in basally branching animals. Finally, we reveal how the study of multigene families may be helpful to unravel the relationships at the base of the metazoan tree. The PCP pathway antedates the radiation of Porifera and may have arisen in the last common ancestor of animals. Oscarella species now appear as key organisms to understand the ancestral function of PCP

  4. Phosphorylation of the Polarity Protein BASL Differentiates Asymmetric Cell Fate through MAPKs and SPCH.

    PubMed

    Zhang, Ying; Guo, Xiaoyu; Dong, Juan

    2016-11-07

    Cell polarization is commonly used for the regulation of stem cell asymmetric division in both animals and plants. Stomatal development in Arabidopsis, a process that produces breathing pores in the epidermis, requires asymmetric cell division to differentiate highly specialized guard cells while maintaining a stem cell population [1, 2]. The BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) protein exhibits a polarized localization pattern in the cell and is required for differential cell fates resulting from asymmetric cell division [3]. The polarization of BASL is made possible by a positive feedback loop with a canonical mitogen-activated protein kinase (MAPK) pathway that recruits the MAPKK kinase YODA (YDA) and MAPK 6 (MPK6) to the cortical polarity site [4]. Here, we study BASL intracellular dynamics and show that the membrane-associated BASL is slowly replenished at the cortical polarity site and that the mobility is tightly linked to its phosphorylation status. Because BASL polarity is only exhibited by one daughter cell after an asymmetric cell division, we study how BASL differentially functions in the two daughter cells. The YDA MAPK cascade transduces upstream ligand-receptor signaling [5-13] to the transcription factor SPEECHLESS (SPCH), which controls stomatal initiation and is directly suppressed by MPK3/6-mediated phosphorylation [14, 15]. We show that BASL polarization leads to elevated nuclear MPK6 signaling and lowered SPCH abundance in one of the two daughter cells. Therefore, two daughter cells are differentiated by BASL polarity-mediated differential suppression of SPCH, which may provide developmental plasticity in plant stem cell asymmetric cell division (ACD).

  5. The Role of Eolian Processes in Forming Martian Polar Topography

    NASA Astrophysics Data System (ADS)

    Howard, A. D.

    1998-01-01

    The major topographic features of the martian polar layered deposits include the conspicuous spiral troughs, subtle undulations, broad reentrants (chasma) and steep, arcuate scarps, and dune fields. A prominent role for eolian processes in formation of all these features is suggested here.

  6. Tissue-Tissue Interaction-Triggered Calcium Elevation Is Required for Cell Polarization during Xenopus Gastrulation

    PubMed Central

    Shindo, Asako; Hara, Yusuke; Yamamoto, Takamasa S.; Ohkura, Masamichi; Nakai, Junichi; Ueno, Naoto

    2010-01-01

    The establishment of cell polarity is crucial for embryonic cells to acquire their proper morphologies and functions, because cell alignment and intracellular events are coordinated in tissues during embryogenesis according to the cell polarity. Although much is known about the molecules involved in cell polarization, the direct trigger of the process remains largely obscure. We previously demonstrated that the tissue boundary between the chordamesoderm and lateral mesoderm of Xenopus laevis is important for chordamesodermal cell polarity. Here, we examined the intracellular calcium dynamics during boundary formation between two different tissues. In a combination culture of nodal-induced chordamesodermal explants and a heterogeneous tissue, such as ectoderm or lateral mesoderm, the chordamesodermal cells near the boundary frequently displayed intracellular calcium elevation; this frequency was significantly less when homogeneous explants were used. Inhibition of the intracellular calcium elevation blocked cell polarization in the chordamesodermal explants. We also observed frequent calcium waves near the boundary of the dorsal marginal zone (DMZ) dissected from an early gastrula-stage embryo. Optical sectioning revealed that where heterogeneous explants touched, the chordamesodermal surface formed a wedge with the narrow end tucked under the heterogeneous explant. No such configuration was seen between homogeneous explants. When physical force was exerted against a chordamesodermal explant with a glass needle at an angle similar to that created in the explant, or migrating chordamesodermal cells crawled beneath a silicone block, intracellular calcium elevation was frequent and cell polarization was induced. Finally, we demonstrated that a purinergic receptor, which is implicated in mechano-sensing, is required for such frequent calcium elevation in chordamesoderm and for cell polarization. This study raises the possibility that tissue-tissue interaction generates

  7. Tissue-tissue interaction-triggered calcium elevation is required for cell polarization during Xenopus gastrulation.

    PubMed

    Shindo, Asako; Hara, Yusuke; Yamamoto, Takamasa S; Ohkura, Masamichi; Nakai, Junichi; Ueno, Naoto

    2010-02-02

    The establishment of cell polarity is crucial for embryonic cells to acquire their proper morphologies and functions, because cell alignment and intracellular events are coordinated in tissues during embryogenesis according to the cell polarity. Although much is known about the molecules involved in cell polarization, the direct trigger of the process remains largely obscure. We previously demonstrated that the tissue boundary between the chordamesoderm and lateral mesoderm of Xenopus laevis is important for chordamesodermal cell polarity. Here, we examined the intracellular calcium dynamics during boundary formation between two different tissues. In a combination culture of nodal-induced chordamesodermal explants and a heterogeneous tissue, such as ectoderm or lateral mesoderm, the chordamesodermal cells near the boundary frequently displayed intracellular calcium elevation; this frequency was significantly less when homogeneous explants were used. Inhibition of the intracellular calcium elevation blocked cell polarization in the chordamesodermal explants. We also observed frequent calcium waves near the boundary of the dorsal marginal zone (DMZ) dissected from an early gastrula-stage embryo. Optical sectioning revealed that where heterogeneous explants touched, the chordamesodermal surface formed a wedge with the narrow end tucked under the heterogeneous explant. No such configuration was seen between homogeneous explants. When physical force was exerted against a chordamesodermal explant with a glass needle at an angle similar to that created in the explant, or migrating chordamesodermal cells crawled beneath a silicone block, intracellular calcium elevation was frequent and cell polarization was induced. Finally, we demonstrated that a purinergic receptor, which is implicated in mechano-sensing, is required for such frequent calcium elevation in chordamesoderm and for cell polarization. This study raises the possibility that tissue-tissue interaction generates

  8. Auxin-regulated cell polarity: an inside job?

    PubMed

    Kramer, Eric M

    2009-05-01

    Auxin is now known to be a key regulator of polar events in plant cells. The mechanism by which auxin conveys a polar signal to the cell is unknown, but one well-known hypothesis is that the auxin flux across the plasma membrane regulates vesicle trafficking. This hypothesis remains controversial because of its reliance on an as-yet-undiscovered membrane flux sensor. In this article I suggest instead that the polar signal is the auxin gradient within the cell cytoplasm. A computer model of vascular development is presented that demonstrates the plausibility of this scenario. The auxin-binding protein ABP1 might be the receptor for the auxin gradient.

  9. Hemispheric Observations of Ionospheric Processes in the Polar Regions

    NASA Astrophysics Data System (ADS)

    Baker, J. B. H.; Ruohoniemi, J. M.; Maimaiti, M.; Thomas, E. G.

    2016-12-01

    Capabilities to monitor ionospheric processes in the polar regions have been significantly improved in recent years by expansion of ground-based instrument networks distributed over hemispheric spatial scales. For example, construction of several new radars at high latitudes (e.g. PolarDARN and RISR) are providing exciting new opportunities to monitor dayside magnetosphere-ionosphere coupling processes poleward of the cusp, particularly during extreme northward IMF conditions. Together with the increasingly dense coverage of GNSS receivers these new radars are also providing valuable new insights about the role of the convection electric field in shaping high latitude ionospheric density features such as polar cap patches and the Tongue of Ionization (TOI). In addition, AMPERE measurements of region-1 and region-2 field-aligned currents can be used to monitor coupled magnetosphere-ionosphere dynamics during storms and substorms, uninterrupted, and in both hemispheres simultaneously. In this presentation, we discuss several case study examples which illustrate how spatially distributed datasets are fundamentally changing our understanding of magnetosphere-ionosphere coupling processes in the polar regions.

  10. Ratiometric fluorescence imaging of cellular polarity: decrease in mitochondrial polarity in cancer cells.

    PubMed

    Jiang, Na; Fan, Jiangli; Xu, Feng; Peng, Xiaojun; Mu, Huiying; Wang, Jingyun; Xiong, Xiaoqing

    2015-02-16

    Mitochondrial polarity strongly influences the intracellular transportation of proteins and interactions between biomacromolecules. The first fluorescent probe capable of the ratiometric imaging of mitochondrial polarity is reported. The probe, termed BOB, has two absorption maxima (λabs = 426 and 561 nm) and two emission maxima--a strong green emission (λem = 467 nm) and a weak red emission (642 nm in methanol)--when excited at 405 nm. However, only the green emission is markedly sensitive to polarity changes, thus providing a ratiometric fluorescence response with a good linear relationship in both extensive and narrow ranges of solution polarity. BOB possesses high specificity to mitochondria (Rr =0.96) that is independent of the mitochondrial membrane potential. The mitochondrial polarity in cancer cells was found to be lower than that of normal cells by ratiometric fluorescence imaging with BOB. The difference in mitochondrial polarity might be used to distinguish cancer cells from normal cells.

  11. Process and apparatus for measuring degree of polarization and angle of major axis of polarized beam of light

    DOEpatents

    Decker, Derek E.; Toeppen, John S.

    1994-01-01

    Apparatus and process are disclosed for calibrating measurements of the phase of the polarization of a polarized beam and the angle of the polarized optical beam's major axis of polarization at a diagnostic point with measurements of the same parameters at a point of interest along the polarized beam path prior to the diagnostic point. The process is carried out by measuring the phase angle of the polarization of the beam and angle of the major axis at the point of interest, using a rotatable polarizer and a detector, and then measuring these parameters again at a diagnostic point where a compensation apparatus, including a partial polarizer, which may comprise a stack of glass plates, is disposed normal to the beam path between a rotatable polarizer and a detector. The partial polarizer is then rotated both normal to the beam path and around the axis of the beam path until the detected phase of the beam polarization equals the phase measured at the point of interest. The rotatable polarizer at the diagnostic point may then be rotated manually to determine the angle of the major axis of the beam and this is compared with the measured angle of the major axis of the beam at the point of interest during calibration. Thereafter, changes in the polarization phase, and in the angle of the major axis, at the point of interest can be monitored by measuring the changes in these same parameters at the diagnostic point.

  12. Density dependent polarized secretion of a prostatic epithelial cell line.

    PubMed

    Djakiew, D; Pflug, B; Delsite, R; Lynch, J H; Onoda, M

    1992-01-01

    The polarized secretions (apical/basal) of newly synthesized total protein and proteases from prostatic epithelial sheets of PA-III cells grown in dual compartment chambers were investigated at various cell densities and culture conditions. PA-III cells grown in a serum free defined medium (SFDM) form morphologically polarized monolayers of epithelial cells. These cells secreted their 35S-methionine labeled total protein in a predominantly apical direction (apical/basal ratio, 4-8 fold), with a lesser proportion of protein secreted apically at lower cell densities of the PA-III cell monolayer. PA-III cells grown in 5% fetal calf serum (FCS) are morphologically squamous, comparable to the anaplastic phenotype, and exhibited an inversion of polarized total protein secretion (apical/basal ratio, 0.4-0.9 fold), with an increased proportion of total protein secreted in a basal direction at lower cell densities. Since the culture of PA-III cells in FCS may approximate the anaplastic phenotype we investigated the polarized secretion of proteases from these cells at various cell densities, and compared them with the secretory pattern of protease secretion from polarized PA-III cells cultured in SFDM. At lower cell densities of the PA-III cells grown in FCS the polarity of protease secretion was inverted such that metalloproteinases, tissue type plasminogen activator, and a 72 kD gelatinase were secreted in a predominantly basal direction, as well as urokinase and a gelatinase of 26 kD that were secreted more or less equally into the apical and basal compartments of the chambers. On the other hand, for cultures of PA-III cells grown in SFDM the aforementioned proteases exhibited predominantly an apically directed polarity of secretion. These results suggest that the anaplastic phenotype characterized by a loss of polarized structure may also be characterized by a functional loss or inversion of polarized secretion. The consequences of such a loss or inversion of polarized

  13. How polarity shapes the destiny of T cells.

    PubMed

    Russell, Sarah

    2008-01-15

    The differentiation, activation and expansion of T cells are dictated by their integrated response to a complex array of extracellular signals. Recent studies provide insight into how these signals are integrated and demonstrate a key role for cell shape in many aspects of T-cell signalling. T cells polarise during migration, antigen presentation and cell division to give rise to daughter cells that can have different cell fates. In each case, the polarity of the T cell facilitates this activity. This raises the possibility that adoption of a polarised state acts as a positive feedback mechanism to enhance responses to specific signals. Similarly, in asymmetric division of other cell types, the distribution of different molecules into each daughter can have profound consequences for proliferation, death and differentiation. The mechanisms of polarity regulation are far better understood in cells such as epithelial cells, neurons and neuronal precursors, and the fertilised zygote. With the emerging parallels between polarity in these cells and T cells, we should now be able to elucidate how polarity affects signalling and cell fate determination in T cells.

  14. The acetylenic tricyclic bis(cyano enone), TBE-31, targets microtubule dynamics and cell polarity in migrating cells.

    PubMed

    Chan, Eddie; Saito, Akira; Honda, Tadashi; Di Guglielmo, Gianni M

    2016-04-01

    Cell migration is dependent on the microtubule network for structural support as well as for the proper delivery and positioning of polarity proteins at the leading edge of migrating cells. Identification of drugs that target cytoskeletal-dependent cell migration and protein transport in polarized migrating cells is important in understanding the cell biology of normal and tumor cells and can lead to new therapeutic targets in disease processes. Here, we show that the tricyclic compound TBE-31 directly binds to tubulin and interferes with microtubule dynamics, as assessed by end binding 1 (EB1) live cell imaging. Interestingly, this interference is independent of in vitro tubulin polymerization. Using immunofluorescence microscopy, we also observed that TBE-31 interferes with the polarity of migratory cells. The polarity proteins Rac1, IQGAP and Tiam1 were localized at the leading edge of DMSO-treated migrating cell, but were observed to be in multiple protrusions around the cell periphery of TBE-31-treated cells. Finally, we observed that TBE-31 inhibits the migration of Rat2 fibroblasts with an IC50 of 0.75 μM. Taken together, our results suggest that the inhibition of cell migration by TBE-31 may result from the improper maintenance of cell polarity of migrating cells.

  15. Cell polarity proteins: common targets for tumorigenic human viruses

    PubMed Central

    Javier, RT

    2012-01-01

    Loss of polarity and disruption of cell junctions are common features of epithelial-derived cancer cells, and mounting evidence indicates that such defects have a direct function in the pathology of cancer. Supporting this idea, results with several different human tumor viruses indicate that their oncogenic potential depends in part on a common ability to inactivate key cell polarity proteins. For example, adenovirus (Ad) type 9 is unique among human Ads by causing exclusively estrogen-dependent mammary tumors in experimental animals and in having E4 region-encoded open reading frame 1 (E4-ORF1) as its primary oncogenic determinant. The 125-residue E4-ORF1 protein consists of two separate protein-interaction elements, one of which defines a PDZ domain-binding motif (PBM) required for E4-ORF1 to induce both cellular transformation in vitro and tumorigenesis in vivo. Most notably, the E4-ORF1 PBM mediates interactions with a selected group of cellular PDZ proteins, three of which include the cell polarity proteins Dlg1, PATJ and ZO-2. Data further indicate that these interactions promote disruption of cell junctions and a loss of cell polarity. In addition, one or more of the E4-ORF1-interacting cell polarity proteins, as well as the cell polarity protein Scribble, are common targets for the high-risk human papillomavirus (HPV) E6 or human T-cell leukemia virus type 1 (HTLV-1) Tax oncoproteins. Underscoring the significance of these observations, in humans, high-risk HPV and HTLV-1 are causative agents for cervical cancer and adult T-cell leukemia, respectively. Consequently, human tumor viruses should serve as powerful tools for deciphering mechanisms whereby disruption of cell junctions and loss of cell polarity contribute to the development of many human cancers. This review article discusses evidence supporting this hypothesis, with an emphasis on the human Ad E4-ORF1 oncoprotein. PMID:19029943

  16. Modified Polar-Format Software for Processing SAR Data

    NASA Technical Reports Server (NTRS)

    Chen, Curtis

    2003-01-01

    HMPF is a computer program that implements a modified polar-format algorithm for processing data from spaceborne synthetic-aperture radar (SAR) systems. Unlike prior polar-format processing algorithms, this algorithm is based on the assumption that the radar signal wavefronts are spherical rather than planar. The algorithm provides for resampling of SAR pulse data from slant range to radial distance from the center of a reference sphere that is nominally the local Earth surface. Then, invoking the projection-slice theorem, the resampled pulse data are Fourier-transformed over radial distance, arranged in the wavenumber domain according to the acquisition geometry, resampled to a Cartesian grid, and inverse-Fourier-transformed. The result of this process is the focused SAR image. HMPF, and perhaps other programs that implement variants of the algorithm, may give better accuracy than do prior algorithms for processing strip-map SAR data from high altitudes and may give better phase preservation relative to prior polar-format algorithms for processing spotlight-mode SAR data.

  17. Cell Polarity: Spot-On Cdc42 Polarization Achieved on Demand.

    PubMed

    Goryachev, Andrew B; Leda, Marcin

    2017-08-21

    A new study deploys optogenetics to induce the yeast bud on demand, at a site determined by a laser spot. The authors definitively prove that the initiation of cell polarization is driven by the Bem1-mediated positive feedback loop and reveal novel features of its regulation by the cell cycle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neo-Vascularization

    PubMed Central

    Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A.; Eichmann, Anne

    2015-01-01

    Background Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Methods and Results Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2 and VEGF induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, as well as pathological ocular neovascularization and wound healing. Conclusions These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2 and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. PMID:26659946

  19. Model of polarization and bistability of cell fragments.

    PubMed

    Kozlov, Michael M; Mogilner, Alex

    2007-12-01

    Directed cell motility is preceded by cell polarization-development of a front-rear asymmetry of the cytoskeleton and the cell shape. Extensive studies implicated complex spatial-temporal feedbacks between multiple signaling pathways in establishing cell polarity, yet physical mechanisms of this phenomenon remain elusive. Based on observations of lamellipodial fragments of fish keratocyte cells, we suggest a purely thermodynamic (not involving signaling) quantitative model of the cell polarization and bistability. The model is based on the interplay between pushing force exerted by F-actin polymerization on the cell edges, contractile force powered by myosin II across the cell, and elastic tension in the cell membrane. We calculate the thermodynamic work produced by these intracellular forces, and show that on the short timescale, the cell mechanics can be characterized by an effective energy profile with two minima that describe two stable states separated by an energy barrier and corresponding to the nonpolarized and polarized cells. Cell dynamics implied by this energy profile is bistable-the cell is either disk-shaped and stationary, or crescent-shaped and motile-with a possible transition between them upon a finite external stimulus able to drive the system over the macroscopic energy barrier. The model accounts for the observations of the keratocyte fragments' behavior and generates quantitative predictions about relations between the intracellular forces' magnitudes and the cell geometry and motility.

  20. Adhesion GPCRs Govern Polarity of Epithelia and Cell Migration.

    PubMed

    Strutt, David; Schnabel, Ralf; Fiedler, Franziska; Prömel, Simone

    2016-01-01

    In multicellular organisms cells spatially arrange in a highly coordinated manner to form tissues and organs, which is essential for the function of an organism. The component cells and resulting structures are often polarised in one or more axes, and how such polarity is established and maintained correctly has been one of the major biological questions for many decades. Research progress has shown that many adhesion GPCRs (aGPCRs) are involved in several types of polarity. Members of the two evolutionarily oldest groups, Flamingo/Celsr and Latrophilins, are key molecules in planar cell polarity of epithelia or the propagation of cellular polarity in the early embryo, respectively. Other adhesion GPCRs play essential roles in cell migration, indicating that this receptor class includes essential molecules for the control of various levels of cellular organisation.

  1. Singularity in polarization: rewiring yeast cells to make two buds.

    PubMed

    Howell, Audrey S; Savage, Natasha S; Johnson, Sam A; Bose, Indrani; Wagner, Allison W; Zyla, Trevin R; Nijhout, H Frederik; Reed, Michael C; Goryachev, Andrew B; Lew, Daniel J

    2009-11-13

    For budding yeast to ensure formation of only one bud, cells must polarize toward one, and only one, site. Polarity establishment involves the Rho family GTPase Cdc42, which concentrates at polarization sites via a positive feedback loop. To assess whether singularity is linked to the specific Cdc42 feedback loop, we disabled the yeast cell's endogenous amplification mechanism and synthetically rewired the cells to employ a different positive feedback loop. Rewired cells violated singularity, occasionally making two buds. Even cells that made only one bud sometimes initiated two clusters of Cdc42, but then one cluster became dominant. Mathematical modeling indicated that, given sufficient time, competition between clusters would promote singularity. In rewired cells, competition occurred slowly and sometimes failed to develop a single "winning" cluster before budding. Slowing competition in normal cells also allowed occasional formation of two buds, suggesting that singularity is enforced by rapid competition between Cdc42 clusters.

  2. Polarization and molecular information transmission in the cell

    NASA Astrophysics Data System (ADS)

    Valdez-Gomez, Adriano; Ramirez-Santiago, Guillermo

    2012-02-01

    During chemotaxis, pseudopodia are extended at the leading edge and retracted at the back of the cell. Efficient chemotaxis is the result of a refined interplay between signaling modules to transmit and integrate spatial information such as PtdIns(3,4,5)P3. The localization of PtdIns(3,4,5)P3 is expected to depend on the distributions or activities of PI3Ks, PTEN, and 5-phosphatases. The spatial signals spread relatively slowly so that high local concentrations of PIP3 in the plasma membrane appear in patches. These gradients induce localization of PIP3 and PTEN to the front and back of the cell, respectively. To simulate this polarization process that involves the action of seven reaction-channels inside the cell we carried out extensive stochastic simulations using Gilliespie algorithm. The simulations were done on a square cell with ten thousand sites (100x100) emulating a square cell with side 10>μm long. We found that there are localized patches of PIP3 at the active receptors and segregation of PTEN on the opposite side of the cell. When we block the reaction-channel, PTEN + PIP3 ->PIP2 that involves the production of PIP2 we obtained a five-fold increase in the concentration of PIP3. This finding appears to be consistent with the o

  3. PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front

    PubMed Central

    Nguyen, Trang Thi Thu; Park, Wei Sun; Park, Byung Ouk; Kim, Cha Yeon; Oh, Yohan; Kim, Jin Man; Choi, Hana; Kyung, Taeyoon; Kim, Cheol-Hee; Lee, Gabsang; Hahn, Klaus M.; Meyer, Tobias; Heo, Won Do

    2016-01-01

    Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. Optogenetic inactivation of PLEKHG3 showed that PLEKHG3 is indispensable both for inducing and for maintaining cell polarity. By selectively binding to newly polymerized actin, PLEKHG3 promotes local Rac1/Cdc42 activation to induce more local actin polymerization, which in turn promotes the recruitment of more PLEKHG3 to induce and maintain cell front. Thus, autocatalytic reinforcement of PLEKHG3 localization to the leading edge of the cell provides a molecular basis for the proposed positive feedback loop that is required for cell polarization and directed migration. PMID:27555588

  4. Ion pump sorting in polarized renal epithelial cells.

    PubMed

    Caplan, M J

    2001-08-01

    The plasma membranes of renal epithelial cells are divided into distinct apical and basolateral domains, which contain different inventories of ion transport proteins. Without this polarity vectorial ion and fluid transport would not be possible. Little is known of the signals and mechanisms that renal epithelial cells use to establish and maintain polarized distributions of their ion transport proteins. Analysis of ion pump sorting reveals that multiple complex signals participate in determining and regulating these proteins' subcellular localizations.

  5. Identification of the Molecular Determinants of Breast Epithelial Cell Polarity

    DTIC Science & Technology

    2004-10-01

    most apical part of lateral membranes, indicating that apico-basal polarity is established even in malignant T4 cells. In 3D lrBM culture, desmosomes ...and hemidesmosomes are highly visible in lateral and basal domains of S I cells, respectively. On the other hand, desmosomes and hemidesmosomes are...restored distinct localizations of desmosomes and hemidesmosomes and thus established basal polarity. TJs are difficult to identify in Fig. 3B as they are

  6. Cell polarity in filamentous fungi: shaping the mold.

    PubMed

    Harris, Steven D

    2006-01-01

    The formation of highly polarized hyphae that grow by apical extension is a defining feature of the filamentous fungi. High-resolution microscopy and mathematical modeling have revealed the importance of the cytoskeleton and the Spitzenkorper (an apical vesicle cluster) in hyphal morphogenesis. However, the underlying molecular mechanisms remain poorly characterized. In this review, the pathways and functions known to be involved in polarized hyphal growth are summarized. A central theme is the notion that the polarized growth of hyphae is more complex than in yeast, though similar sets of core pathways are likely utilized. In addition, a model for the establishment and maintenance of hyphal polarity is presented. Key features of the model include the idea that polarity establishment is a stochastic process that occurs independent of internal landmarks. Moreover, the stabilization of nascent polarity axes may be the critical step that permits the emergence of a new hypha.

  7. Postnatal refinement of auditory hair cell planar polarity deficits occurs in the absence of Vangl2.

    PubMed

    Copley, Catherine O; Duncan, Jeremy S; Liu, Chang; Cheng, Haixia; Deans, Michael R

    2013-08-28

    The distinctive planar polarity of auditory hair cells is evident in the polarized organization of the stereociliary bundle. Mutations in the core planar cell polarity gene Van Gogh-like 2 (Vangl2) result in hair cells that fail to properly orient their stereociliary bundles along the mediolateral axis of the cochlea. The severity of this phenotype is graded along the length of the cochlea, similar to the hair cell differentiation gradient, suggesting that an active refinement process corrects planar polarity phenotypes in Vangl2 knock-out (KO) mice. Because Vangl2 gene deletions are lethal, Vangl2 conditional knock-outs (CKOs) were generated to test this hypothesis. When crossed with Pax2-Cre, Vangl2 is deleted from the inner ear, yielding planar polarity phenotypes similar to Vangl2 KOs at late embryonic stages except that Vangl2 CKO mice are viable and do not have craniorachischisis like Vangl2 KOs. Quantification of planar polarity deficits through postnatal development demonstrates the activity of a Vangl2-independent refinement process that rescues the planar polarity phenotype within 10 d of birth. In contrast, the Pax2-Cre;Vangl2 CKO has profound changes in the shape and distribution of outer pillar cell and Deiters' cell phalangeal processes that are not corrected during the period of planar polarity refinement. Auditory brainstem response analyses of adult mice show a 10-15 dB shift in auditory threshold, and distortion product otoacoustic emission measurements indicate that this mild hearing deficit is of cochlear origin. Together, these data demonstrate a Vangl2-independent refinement mechanism that actively reorients auditory stereociliary bundles and reveals an unexpected role of Vangl2 during supporting cell morphogenesis.

  8. Postnatal Refinement of Auditory Hair Cell Planar Polarity Deficits Occurs in the Absence of Vangl2

    PubMed Central

    Copley, Catherine O.; Duncan, Jeremy S.; Liu, Chang; Cheng, Haixia

    2013-01-01

    The distinctive planar polarity of auditory hair cells is evident in the polarized organization of the stereociliary bundle. Mutations in the core planar cell polarity gene Van Gogh-like 2 (Vangl2) result in hair cells that fail to properly orient their stereociliary bundles along the mediolateral axis of the cochlea. The severity of this phenotype is graded along the length of the cochlea, similar to the hair cell differentiation gradient, suggesting that an active refinement process corrects planar polarity phenotypes in Vangl2 knock-out (KO) mice. Because Vangl2 gene deletions are lethal, Vangl2 conditional knock-outs (CKOs) were generated to test this hypothesis. When crossed with Pax2–Cre, Vangl2 is deleted from the inner ear, yielding planar polarity phenotypes similar to Vangl2 KOs at late embryonic stages except that Vangl2 CKO mice are viable and do not have craniorachischisis like Vangl2 KOs. Quantification of planar polarity deficits through postnatal development demonstrates the activity of a Vangl2-independent refinement process that rescues the planar polarity phenotype within 10 d of birth. In contrast, the Pax2–Cre;Vangl2 CKO has profound changes in the shape and distribution of outer pillar cell and Deiters' cell phalangeal processes that are not corrected during the period of planar polarity refinement. Auditory brainstem response analyses of adult mice show a 10–15 dB shift in auditory threshold, and distortion product otoacoustic emission measurements indicate that this mild hearing deficit is of cochlear origin. Together, these data demonstrate a Vangl2-independent refinement mechanism that actively reorients auditory stereociliary bundles and reveals an unexpected role of Vangl2 during supporting cell morphogenesis. PMID:23986237

  9. Release of simian virus 40 virions from epithelial cells is polarized and occurs without cell lysis.

    PubMed Central

    Clayson, E T; Brando, L V; Compans, R W

    1989-01-01

    We have investigated the process of release of simian virus 40 (SV40) virions from several monkey kidney cell lines. High levels of virus release were observed prior to any significantly cytopathic effects in all cell lines examined, indicating that SV40 utilizes a mechanism for escape from the host cell which does not involve cell lysis. We demonstrate that SV40 release was polarized in two epithelial cell types (Vero C1008 and primary African green monkey kidney cells) grown on permeable supports; release of virus occurs almost exclusively at apical surfaces. In contrast, equivalent amounts of SV40 virions were recovered from apical and basal culture fluids of nonpolarized CV-1 cells. SV40 virions were observed in large numbers on apical surfaces of epithelial cells and in cytoplasmic smooth membrane vesicles. The sodium ionophore monensin, an inhibitor of vesicular transport, was found to inhibit SV40 release without altering viral protein synthesis or infectious virus production. Images PMID:2539518

  10. Fully solution-processed, transparent organic power-generating polarizer

    NASA Astrophysics Data System (ADS)

    Chou, Wei-Yu; Hsu, Fang-Chi; Chen, Yang-Fang

    2017-03-01

    We fabricate transparent organic power-generating polarizer by all solution process. Based on the conventional indium–tin-oxide-coated glass as the bottom cathode, the subsequent layers are prepared by a combination of solution processing methods. Sprayed silver nanowires film serves as the top anode and can transmit greater than 80% of the visible light with sheet resistance of 16 Ω/□. By adopting the quasi-bilayer structure for the photoactive layer composed of rubbed polymer donors to produce anisotropic optical property underneath fullerene acceptors, the finished device demonstrates a power conversion efficiency of 1.36% with unpolarized light, a dichroic ratio of 3.2, and a high short circuit current ratio of 2.6 with polarized light. Our proposed fabrication procedures of devices take into account not only the cost-effective production, but also the flexibility of devices for applying in flexible, scalable circuits to advance the development of future technology.

  11. The tumor suppressor Lgl1 regulates front-rear polarity of migrating cells.

    PubMed

    Ravid, Shoshana

    2014-01-01

    Cell migration is a highly integrated, multistep process that plays an important role in physiological and pathological processes. The migrating cell is highly polarized, with complex regulatory pathways that integrate its component processes spatially and temporally. The Drosophila tumor suppressor, Lethal (2) giant larvae (Lgl), regulates apical-basal polarity in epithelia and asymmetric cell division. But little is known about the role of Lgl in establishing cell polarity in migrating cells. Recently, we showed that the mammalian Lgl1 interacts directly with non-muscle myosin IIA (NMIIA), inhibiting its ability to assemble into filaments in vitro. Lgl1 also regulates the cellular localization of NMIIA, the maturation of focal adhesions, and cell migration. We further showed that phosphorylation of Lgl1 by aPKCζ prevents its interaction with NMIIA and is important for Lgl1 and acto-NMII cytoskeleton cellular organization. Lgl is a critical downstream target of the Par6-aPKC cell polarity complex; we showed that Lgl1 forms two distinct complexes in vivo, Lgl1-NMIIA and Lgl1-Par6-aPKCζ in different cellular compartments. We further showed that aPKCζ and NMIIA compete to bind directly to Lgl1 through the same domain. These data provide new insights into the role of Lgl1, NMIIA, and Par6-aPKCζ in establishing front-rear polarity in migrating cells. In this commentary, I discuss the role of Lgl1 in the regulation of the acto-NMII cytoskeleton and its regulation by the Par6-aPKCζ polarity complex, and how Lgl1 activity may contribute to the establishment of front-rear polarity in migrating cells.

  12. Polarization processes in rocks: 2. Complex Dielectric Permittivity method

    NASA Astrophysics Data System (ADS)

    Levitskaya, Tsylya M.; Sternberg, Ben K.

    1996-07-01

    This is the second part of a review of research performed in the former USSR. Experimental data were used from several regions of the USSR, including Russia, Ukraine, and Georgia. Many of the publications are available in U.S. libraries. Some of them are translated into English. This part considers results of studying rocks with the Complex Electrical Resistivity method, primarily in the frequency range from 0.01 Hz to 50 MHz. Results of studying polarization processes in sedimentary rocks of different lithology and porosity with different types of saturation (salt solutions of various salinity and hydrocarbons) are described. Laboratory studies of ore-mineral containing rocks are also considered. Describing the measurement methods, we have placed primary emphasis on means for avoiding or reducing the electrode polarization effects. It is shown that wet rocks may have two polarization processes: one at low frequencies, below 1 Hz, and one at high frequencies, above 10 kHz. The mechanisms of these processes are discussed based on experimental results.

  13. The second touch hypothesis: T cell activation, homing and polarization.

    PubMed

    Ley, Klaus

    2014-01-01

    The second touch hypothesis states that T cell activation, proliferation, induction of homing receptors and polarization are distinguishable and, at least in part, sequential. The second touch hypothesis maintains that full T cell polarization requires T cell interaction with antigen-presenting cells (DCs, macrophages, B cells and certain activated stromal cells) in the non-lymphoid tissue where the antigen resides. Upon initial antigen encounter in peripheral lymph nodes (PLN), T cells become activated, proliferate and express homing receptors that enable them to recirculate to the (inflamed) tissue that contains the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and induced regulatory T cells (iTreg) requires additional antigen presentation by tissue macrophages and other antigen presenting cells (APCs) in the inflamed tissue. Here, I present a conceptual framework for the importance of peripheral (non-lymphoid) antigen presentation to antigen-experienced T cells.

  14. Data processing workflow for time of flight polarized neutrons inelastic measurements

    NASA Astrophysics Data System (ADS)

    Savici, Andrei T.; Zaliznyak, Igor A.; Ovidiu Garlea, V.; Winn, Barry

    2017-06-01

    We discuss the data processing workflow for polarized neutron scattering measurements performed at HYSPEC [1] spectrometer at the Spallation Neutron Source, Oak Ridge National Laboratory. The effects of the focusing Heusler crystal polarizer and the wide- angle supermirror transmission polarization analyzer are added to the data processing flow of the non-polarized case. The implementation is done using the Mantid [2] software package.

  15. Data processing workflow for time of flight polarized neutrons inelastic measurements

    SciTech Connect

    Savici, Andrei T; Zaliznyak, Igor; Garlea, Vasile O; Winn, Barry L

    2017-01-01

    We discuss the data processing workflow for polarized neutron scattering measurements performed at HYSPEC spectrometer at the Spallation Neutron Source, Oak Ridge National Laboratory. The effects of the focusing Heusler crystal polarizer and the wide-angle supermirror transmission polarization analyzer are added to the data processing flow of the non-polarized case. The implementation is done using the Mantid software package.

  16. An on-chip study on the influence of geometrical confinement and chemical gradient on cell polarity.

    PubMed

    Zheng, Wenfu; Xie, Yunyan; Sun, Kang; Wang, Dong; Zhang, Yi; Wang, Chen; Chen, Yong; Jiang, Xingyu

    2014-09-01

    Cell polarity plays key roles in tissue development, regeneration, and pathological processes. However, how the cells establish and maintain polarity is still obscure so far. In this study, by employing microfluidic techniques, we explored the influence of geometrical confinement and chemical stimulation on the cell polarity and their interplay. We found that teardrop shape-induced anterior/posterior polarization of cells displayed homogeneous distribution of epidermal growth factor receptor, and the polarity could be maintained in a uniform epidermal growth factor (EGF) solution, but be broken by a reverse gradient of EGF, implying different mechanism of geometrical and chemical cue-induced cell polarity. Further studies indicated that a teardrop pattern could cause polarized distribution of microtubule-organization center and nucleus-Golgi complex, and this polarity was weakened when the cells were released from the confinement. Our study provides the evidence regarding the difference between geometrical and chemical cue-induced cell polarity and would be useful for understanding relationship between polarity and directional migration of cells.

  17. Reciprocal and dynamic polarization of planar cell polarity core components and myosin

    PubMed Central

    Newman-Smith, Erin; Kourakis, Matthew J; Reeves, Wendy; Veeman, Michael; Smith, William C

    2015-01-01

    The Ciona notochord displays planar cell polarity (PCP), with anterior localization of Prickle (Pk) and Strabismus (Stbm). We report that a myosin is polarized anteriorly in these cells and strongly colocalizes with Stbm. Disruption of the actin/myosin machinery with cytochalasin or blebbistatin disrupts polarization of Pk and Stbm, but not of myosin complexes, suggesting a PCP-independent aspect of myosin localization. Wash out of cytochalasin restored Pk polarization, but not if done in the presence of blebbistatin, suggesting an active role for myosin in core PCP protein localization. On the other hand, in the pk mutant line, aimless, myosin polarization is disrupted in approximately one third of the cells, indicating a reciprocal action of core PCP signaling on myosin localization. Our results indicate a complex relationship between the actomyosin cytoskeleton and core PCP components in which myosin is not simply a downstream target of PCP signaling, but also required for PCP protein localization. DOI: http://dx.doi.org/10.7554/eLife.05361.001 PMID:25866928

  18. A Predictive Model for Yeast Cell Polarization in Pheromone Gradients.

    PubMed

    Muller, Nicolas; Piel, Matthieu; Calvez, Vincent; Voituriez, Raphaël; Gonçalves-Sá, Joana; Guo, Chin-Lin; Jiang, Xingyu; Murray, Andrew; Meunier, Nicolas

    2016-04-01

    Budding yeast cells exist in two mating types, a and α, which use peptide pheromones to communicate with each other during mating. Mating depends on the ability of cells to polarize up pheromone gradients, but cells also respond to spatially uniform fields of pheromone by polarizing along a single axis. We used quantitative measurements of the response of a cells to α-factor to produce a predictive model of yeast polarization towards a pheromone gradient. We found that cells make a sharp transition between budding cycles and mating induced polarization and that they detect pheromone gradients accurately only over a narrow range of pheromone concentrations corresponding to this transition. We fit all the parameters of the mathematical model by using quantitative data on spontaneous polarization in uniform pheromone concentration. Once these parameters have been computed, and without any further fit, our model quantitatively predicts the yeast cell response to pheromone gradient providing an important step toward understanding how cells communicate with each other.

  19. A Predictive Model for Yeast Cell Polarization in Pheromone Gradients

    PubMed Central

    Calvez, Vincent; Voituriez, Raphaël; Gonçalves-Sá, Joana; Guo, Chin-Lin; Jiang, Xingyu; Murray, Andrew; Meunier, Nicolas

    2016-01-01

    Budding yeast cells exist in two mating types, a and α, which use peptide pheromones to communicate with each other during mating. Mating depends on the ability of cells to polarize up pheromone gradients, but cells also respond to spatially uniform fields of pheromone by polarizing along a single axis. We used quantitative measurements of the response of a cells to α-factor to produce a predictive model of yeast polarization towards a pheromone gradient. We found that cells make a sharp transition between budding cycles and mating induced polarization and that they detect pheromone gradients accurately only over a narrow range of pheromone concentrations corresponding to this transition. We fit all the parameters of the mathematical model by using quantitative data on spontaneous polarization in uniform pheromone concentration. Once these parameters have been computed, and without any further fit, our model quantitatively predicts the yeast cell response to pheromone gradient providing an important step toward understanding how cells communicate with each other. PMID:27077831

  20. Carbon Dioxide Convection in the Martian Polar Night and Its Implications for Polar Processes

    NASA Technical Reports Server (NTRS)

    Colaprete, A.; Haberle, R. M.

    2003-01-01

    Each Martian year nearly 30% of the atmosphere is exchanged with the polar ice caps. This exchange occurs through a combination of direct surface condensation and atmospheric precipitation of carbon dioxide. It has long been thought the amount of condensation within the polar night is maintained by a balance between diabatic processes such as radiative cooling and latent heating from condensing CO2. This assumption manifests itself in Mars General Circulation Models (GCM) in such a way as to never allow the atmospheric temperature to dip below the saturation temperature of CO2. However, observations from Mars Global Surveyor (MGS) Radio Science (RS) and the Thermal Emission Spectrometer (TES) have demonstrated this assumption to be, at best, approximate. Both RS and TES observations within the polar nights of both poles indicate substantial supersaturated regions with respect to CO2. The observed temperature profiles suggest conditionally unstable regions containing planetary significant amounts of potential convective energy. Presented here are estimates of the total planetary inventory of convective available potential energy (CAPE) and the potential convective energy flux (PCEF). The values for CAPE and PCEF are derived from RS temperature profiles and compared to Mars GCM results using a new convective CO2 cloud model that allows for the formation of CAPE.

  1. Polarization and reprogramming of myeloid-derived suppressor cells.

    PubMed

    Yang, Wen-Chin; Ma, Ge; Chen, Shu-Hsia; Pan, Ping-Ying

    2013-06-01

    Myeloid-derived suppressor cells (MDSC) have recently emerged as one of the central regulators of the immune system. In recent years, interest in understanding MDSC biology and applying MDSC for therapeutic purpose has exploded exponentially. Despite recent progress in MDSC biology, the mechanisms underlying MDSC development from expansion and activation to polarization in different diseases remain poorly understood. More recent studies have demonstrated that two MDSC subsets, M (monocytic)-MDSC and G (granulocytic)-MDSC, are able to polarize from a classically activated phenotype (M1) to an alternatively activated one (M2), or vice versa, in tumor-bearing mice. This phenotypic polarization affects MDSC function and disease progression. In this article, we summarize and discuss polarization, mechanism and therapeutic potential of MDSC. An emphasis is placed on the emerging concept of reprogramming MDSC polarization as a therapeutic strategy.

  2. Collective Chemotaxis Requires Contact-Dependent Cell Polarity

    PubMed Central

    Theveneau, Eric; Marchant, Lorena; Kuriyama, Sei; Gull, Mazhar; Moepps, Barbara; Parsons, Maddy; Mayor, Roberto

    2010-01-01

    Summary Directional collective migration is now a widely recognized mode of migration during embryogenesis and cancer. However, how a cluster of cells responds to chemoattractants is not fully understood. Neural crest cells are among the most motile cells in the embryo, and their behavior has been likened to malignant invasion. Here, we show that neural crest cells are collectively attracted toward the chemokine Sdf1. While not involved in initially polarizing cells, Sdf1 directionally stabilizes cell protrusions promoted by cell contact. At this cell contact, N-cadherin inhibits protrusion and Rac1 activity and in turn promotes protrusions and activation of Rac1 at the free edge. These results show a role for N-cadherin during contact inhibition of locomotion, and they reveal a mechanism of chemoattraction likely to function during both embryogenesis and cancer metastasis, whereby attractants such as Sdf1 amplify and stabilize contact-dependent cell polarity, resulting in directional collective migration. PMID:20643349

  3. Llgl1 Connects Cell Polarity with Cell-Cell Adhesion in Embryonic Neural Stem Cells.

    PubMed

    Jossin, Yves; Lee, Minhui; Klezovitch, Olga; Kon, Elif; Cossard, Alexia; Lien, Wen-Hui; Fernandez, Tania E; Cooper, Jonathan A; Vasioukhin, Valera

    2017-06-05

    Malformations of the cerebral cortex (MCCs) are devastating developmental disorders. We report here that mice with embryonic neural stem-cell-specific deletion of Llgl1 (Nestin-Cre/Llgl1(fl/fl)), a mammalian ortholog of the Drosophila cell polarity gene lgl, exhibit MCCs resembling severe periventricular heterotopia (PH). Immunohistochemical analyses and live cortical imaging of PH formation revealed that disruption of apical junctional complexes (AJCs) was responsible for PH in Nestin-Cre/Llgl1(fl/fl) brains. While it is well known that cell polarity proteins govern the formation of AJCs, the exact mechanisms remain unclear. We show that LLGL1 directly binds to and promotes internalization of N-cadherin, and N-cadherin/LLGL1 interaction is inhibited by atypical protein kinase C-mediated phosphorylation of LLGL1, restricting the accumulation of AJCs to the basolateral-apical boundary. Disruption of the N-cadherin-LLGL1 interaction during cortical development in vivo is sufficient for PH. These findings reveal a mechanism responsible for the physical and functional connection between cell polarity and cell-cell adhesion machineries in mammalian cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Polarization of yeast cells in spatial gradients of alpha mating factor.

    PubMed Central

    Segall, J E

    1993-01-01

    The process of cell fusion during mating of the yeast Saccharomyces cerevisiae is mediated by factors secreted by the mating partners. Spatial gradients of one of these mating factors, alpha-factor, polarized the growth of projections by MATa cells. The site of previous budding did not affect the direction of polarization, and subsequent budding was also polarized if mating factor was removed. Orientation occurred in the presence of nocodazole, suggesting that microtubules were not critical. At extremely low concentrations of alpha-factor, sst2-mutants (which in genetic studies do not discriminate between partners producing different amounts of alpha-factor) were able to polarize their projections. The sensitivity of this spatial sensing mechanism in wild-type cells is such that differences in receptor occupancy estimated to be about 1% are sufficient for orientation. Images Fig. 1 Fig. 2 Fig. 3 PMID:8397402

  5. Cell polarity and spindle orientation in the distal epithelium of embryonic lung.

    PubMed

    El-Hashash, Ahmed H; Warburton, David

    2011-02-01

    A proper balance between self-renewal and differentiation of lung-specific progenitors at the distal epithelial tips is absolutely required for normal lung morphogenesis. Cell polarity and mitotic spindle orientation play a critical role in the self-renewal/differentiation of epithelial cells and can impact normal physiological processes, including epithelial tissue branching and differentiation. Therefore, understanding the behavior of lung distal epithelial progenitors could identify innovative solutions to restoring normal lung morphogenesis. Yet little is known about cell polarity, spindle orientation, and segregation of cell fate determinant in the embryonic lung epithelium, which contains progenitor cells. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized and highly mitotic with characteristic perpendicular cell divisions. Consistent with these findings, mInsc, LGN, and NuMA polarity proteins, which control spindle orientation, are asymmetrically localized in mitotic distal epithelial progenitors of embryonic lungs. Furthermore, the cell fate determinant Numb is asymmetrically distributed at the apical side of distal epithelial progenitors and segregated to one daughter cell in most mitotic cells. These findings provide evidence for polarity in distal epithelial progenitors of embryonic lungs and provide a framework for future translationally oriented studies in this area.

  6. Polarization processes in rocks: 1. Complex Dielectric Permittivity method

    NASA Astrophysics Data System (ADS)

    Levitskaya, Tsylya M.; Sternberg, Ben K.

    1996-07-01

    This is the first part of a review of research performed in the former USSR. Experimental data were used from several regions of the USSR, including Russia, Ukraine, and Georgia. Many of the publications are available in U.S. libraries. Some of them are translated into English. This part contains results from applying the Complex Dielectric Permittivity method (Dielectric Spectroscopy) for studying the electrical response of rocks in alternating fields with frequencies from 100 Hz to 100 MHz. Data on dielectric properties of sedimentary rocks of different lithology and with various porosities, salinities of saturating solution, and hydrocarbon content are reviewed here. Measurement methods, including means for avoiding or reducing the electrode polarization, are also considered. It is shown that wet rocks exhibit a Maxwell-Wagner polarization process at frequencies 105-107 Hz, caused by charge accumulation on the pore boundaries.

  7. Polarization modeling and performance optimization of a molten sodium hydroxide direct carbon fuel cell (MHDCFC)

    NASA Astrophysics Data System (ADS)

    Xing, Li; Hao, Jiamao; Li, Xiaofeng; Zhang, Yao; Hu, Zhiguang; Gao, Yanfang

    2017-09-01

    An electrochemical model for a molten sodium hydroxide direct carbon fuel cell (MHDCFC) is developed based on electrochemical reaction dynamics, mass transfer, and electrode processes in the cell. Activated carbon and graphite are considered the main fuels, and static and dynamic parameters describing polarizations are taken into account for valuation and optimization of cell performance. Asymmetric reaction compartments are used in the MHDCFC, and the effect of the anodic compartment height on polarization is described first. The cell performance mainly depends on temperature (T), the pressures in the anodic (Pan) and cathodic compartments (Pcat), the anodic compartment height (H1), and the fuel type. Besides, cell performance is affected by ohmic polarization, anode activation polarization, cathode concentration polarization, and cathode activation polarization, in order of precedence. At Pan of 1.8 atm, Pcat of 1.7 atm, H1 of 0.06 m, and T of 773-973 K, the efficiencies (e) of the cells with activated carbon and graphite are higher than 50% at current densities of 0-500 A m-2 and 0-700 A m-2, respectively. The maximum power densities (e > 50%) are achieved for activated carbon and graphite and reach 367.6626 W m-2 and 498.9687 W m-2, respectively.

  8. Polarity Proteins and Cell–Cell Interactions in the Testis

    PubMed Central

    Wong, Elissa W.P.; Cheng, C. Yan

    2009-01-01

    In mammalian testes, extensive junction restructuring takes place in the seminiferous epithelium at the Sertoli–Sertoli and Sertoli–germ cell interface to facilitate the different cellular events of spermatogenesis, such as mitosis, meiosis, spermiogenesis, and spermiation. Recent studies in the field have shown that Rho GTPases and polarity proteins play significant roles in the events of cell–cell interactions. Furthermore, Rho GTPases, such as Cdc42, are working in concert with polarity proteins in regulating cell polarization and cell adhesion at both the blood–testis barrier (BTB) and apical ectoplasmic specialization (apical ES) in the testis of adult rats. In this chapter, we briefly summarize recent findings on the latest status of research and development regarding Cdc42 and polarity proteins and how they affect cell–cell interactions in the testis and other epithelia. More importantly, we provide a new model in which how Cdc42 and components of the polarity protein complexes work in concert with laminin fragments, cytokines, and testosterone to regulate the events of cell–cell interactions in the seminiferous epithelium via a local autocrine-based regulatory loop known as the apical ES—BTB—basement membrane axis. This new functional axis coordinates various cellular events during different stages of the seminiferous epithelium cycle of spermatogenesis. PMID:19815182

  9. Endomembrane control of cell polarity: Relevance to cancer.

    PubMed

    Baschieri, Francesco; Farhan, Hesso

    2015-01-01

    The role of polarity in cancer is an emerging research area and loss of polarity is widely considered an important event in cancer. Among the polarity regulating molecules, the small GTPase Cdc42 was extensively studied. Most attention was given to Cdc42 signaling at the plasma membrane, but whether and how Cdc42 is regulated at endomembranes remained poorly understood. Moreover, whether the endomembrane pool of Cdc42 is of any relevance to cell polarity was unknown. In our recent work, we identified a complex between the Golgi matrix protein GM130 and RasGRF and showed that it is responsible for regulating the Golgi pool of Cdc42, but had no effect on the plasma membrane pool of Cdc42. Depletion of GM130 disrupted apico-basal polarity as well as front-rear polarity, indicating that the spatial pool of Cdc42 is functionally relevant. The biomedical relevance of this finding was supported by the observation than GM130 is progressively lost in colorectal cancer. These findings support a role of the endomembrane pool of Cdc42 in cell polarity and point to a potential role of alterations of this pool in cancer.

  10. Characterization of PEM fuel cell degradation by polarization change curves

    NASA Astrophysics Data System (ADS)

    Bezmalinovic, Dario; Simic, Boris; Barbir, Frano

    2015-10-01

    Polarization change curves, defined as a difference between the polarization curve at the beginning of life and the actual polarization curve after the cell has been operational for some time, were used to analyze degradation of a PEM fuel cell exposed to voltage cycling as an accelerated stress test for electrocatalyst degradation. Degradation, i.e., loss of voltage was due to increase of activation losses and increase of resistance in the catalyst layer, both most likely due to the loss of catalyst electrochemically active area. The results of the polarization change curves analysis correspond to the findings of the periodic individual tests performed during the accelerated stress test, such as electrochemical impedance spectroscopy, cyclic voltammetry and linear sweep voltammetry. Therefore, this method has potential to be used as a relatively quick and simple, yet effective, degradation diagnostic tool.

  11. Planar Cell Polarity Signaling: The Developing Cell’s Compass

    PubMed Central

    Vladar, Eszter K.; Antic, Dragana; Axelrod, Jeffrey D.

    2009-01-01

    Cells of many tissues acquire cellular asymmetry to execute their physiologic functions. The planar cell polarity system, first characterized in Drosophila, is important for many of these events. Studies in Drosophila suggest that an upstream system breaks cellular symmetry by converting tissue gradients to subcellular asymmetry, whereas a downstream system amplifies subcellular asymmetry and communicates polarity between cells. In this review, we discuss apparent similarities and differences in the mechanism that controls PCP as it has been adapted to a broad variety of morphological cellular asymmetries in various organisms. PMID:20066108

  12. Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells

    PubMed Central

    Cooper, Sam; Sadok, Amine; Bousgouni, Vicky; Bakal, Chris

    2015-01-01

    Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space—an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively. PMID:26310441

  13. Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models

    NASA Astrophysics Data System (ADS)

    Giese, Wolfgang; Eigel, Martin; Westerheide, Sebastian; Engwer, Christian; Klipp, Edda

    2015-12-01

    In silico experiments bear the potential for further understanding of biological transport processes by allowing a systematic modification of any spatial property and providing immediate simulation results. Cell polarization and spatial reorganization of membrane proteins are fundamental for cell division, chemotaxis and morphogenesis. We chose the yeast Saccharomyces cerevisiae as an exemplary model system which entails the shuttling of small Rho GTPases such as Cdc42 and Rho, between an active membrane-bound form and an inactive cytosolic form. We used partial differential equations to describe the membrane-cytosol shuttling of proteins. In this study, a consistent extension of a class of 1D reaction-diffusion systems into higher space dimensions is suggested. The membrane is modeled as a thin layer to allow for lateral diffusion and the cytosol is modeled as an enclosed volume. Two well-known polarization mechanisms were considered. One shows the classical Turing-instability patterns, the other exhibits wave-pinning dynamics. For both models, we investigated how cell shape and diffusion barriers like septin structures or bud scars influence the formation of signaling molecule clusters and subsequent polarization. An extensive set of in silico experiments with different modeling hypotheses illustrated the dependence of cell polarization models on local membrane curvature, cell size and inhomogeneities on the membrane and in the cytosol. In particular, the results of our computer simulations suggested that for both mechanisms, local diffusion barriers on the membrane facilitate Rho GTPase aggregation, while diffusion barriers in the cytosol and cell protrusions limit spontaneous molecule aggregations of active Rho GTPase locally.

  14. Polarized Fluorescence Microscopy to Study Cytoskeleton Assembly and Organization in Live Cells.

    PubMed

    McQuilken, Molly; Mehta, Shalin B; Verma, Amitabh; Harris, Grant; Oldenbourg, Rudolf; Gladfelter, Amy S

    2015-06-01

    The measurement of not only the location but also the organization of molecules in live cells is crucial to understanding diverse biological processes. Polarized light microscopy provides a nondestructive means to evaluate order within subcellular domains. When combined with fluorescence microscopy and GFP-tagged proteins, the approach can reveal organization within specific populations of molecules. This unit describes a protocol for measuring the architectural dynamics of cytoskeletal components using polarized fluorescence microscopy and OpenPolScope open-access software (http://www.openpolscope.org). The protocol describes installation of linear polarizers or a liquid crystal (LC) universal compensator, calibration of the system, polarized fluorescence imaging, and analysis. The use of OpenPolScope software and hardware allows for reliable, user-friendly image acquisition to measure and analyze polarized fluorescence. Copyright © 2015 John Wiley & Sons, Inc.

  15. Polarized Fluorescence Microscopy to Study Cytoskeleton Assembly and Organization in live cells

    PubMed Central

    McQuilken, Molly; Mehta, Shalin B.; Verma, Amitabh; Harris, Grant; Oldenbourg, Rudolf; Gladfelter, Amy S.

    2015-01-01

    The measurement of not only the location but also the organization of molecules in live cells is crucial to understanding diverse biological processes. Polarized light microscopy provides a nondestructive means to evaluate order within subcellular domains. When combined with fluorescence microscopy and GFP-tagged proteins, the approach can reveal organization within specific populations of molecules. This unit describes a protocol for measuring the architectural dynamics of cytoskeletal components using polarized fluorescence microscopy and OpenPolScope open-access software (www.openpolscope.org). The protocol describes installation of linear polarizers or a liquid crystal (LC) universal compensator, calibration of the system, polarized fluorescence imaging, and analysis. The use of OpenPolScope software and hardware allows for reliable, user-friendly image acquisition to measure and analyze polarized fluorescence. PMID:26061244

  16. Balloon cell melanoma: a case report with polarized and non-polarized dermatoscopy and dermatopathology

    PubMed Central

    Maher, James; Cameron, Alan; Wallace, Sharon; Acosta-Rojas, Rafael; Weedon, David; Rosendahl, Cliff

    2014-01-01

    Balloon cell melanoma is a rare melanoma subtype, with only one previous case with dermatoscopy published. It is often non-pigmented, leading to diagnostic difficulty, and there is a tendency for lesions to be thick at diagnosis. We report a case of balloon cell melanoma on the forearm of a 61-year-old man with both polarized and non-polarized dermatoscopy and dermatopathology. It presented as a firm pale nodule with focal eccentric pigmentation. The clinical images evoke a differential diagnosis of dermatofibroma, dermal nevus, Spitz nevus and basal cell carcinoma as well as melanoma. This melanoma was partially pigmented due to a small, pigmented superficial spreading component on the edge of the non-pigmented balloon cell nodule, prompting further evaluation. In retrospect there was the clue to malignancy of polarizing-specific white lines (chrysalis structures) and polymorphous vessels, including a pattern of dot vessels. The reticular lines exclude basal cell carcinoma, polarizing-specific white lines are inconsistent with the diagnosis of dermal nevus and their eccentric location is inconsistent with both Spitz nevus and dermatofibroma. Excision biopsy was performed, revealing a superficial spreading melanoma with two distinct invasive components, one of atypical non-mature epithelioid cells and the other an amelanotic nodular component, comprising more than 50% of the lesion, characterized by markedly distended epithelioid melanocytes showing pseudo-xanthomatous cytoplasmic balloon cell morphology. A diagnosis of balloon cell melanoma, Breslow thickness 1.9 mm, mitotic rate 3 per square millimeter was rendered. Wide local excision was performed, as was sentinel lymph node biopsy, which was negative. PMID:24520518

  17. Loss of GM130 in breast cancer cells and its effects on cell migration, invasion and polarity.

    PubMed

    Baschieri, Francesco; Uetz-von Allmen, Edith; Legler, Daniel F; Farhan, Hesso

    2015-01-01

    Spatially distinct pools of the small GTPase Cdc42 were observed, but the major focus of research so far has been to investigate its signaling at the plasma membrane. We recently showed that the Golgi pool of Cdc42 is relevant for cell polarity and that it is regulated by GM130, a Golgi matrix protein. Loss of GM130 abrogated cell polarity and consistent with the notion that polarity is frequently impaired in cancer, we found that GM130 is downregulated in colorectal cancer. Whether the loss of GM130 solely affects polarity, or whether it affects other processes relevant for tumorigenesis remains unclear. In a panel of breast cancer cells lines, we investigated the consequences of GM130 depletion on traits of relevance for tumor progression, such as survival, proliferation, adhesion, migration and invasion. We show that cellular assays that depend on polarity, such as chemotaxis and wound scratch assays, are only of limited use to investigate the role of polarity modulators in cancer. Depletion of GM130 increases cellular velocity and increases the invasiveness of breast cancer cells, therefore supporting the view that alterations of polarity contribute to tumor progression.

  18. Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

    PubMed Central

    Guillabert-Gourgues, Aude; Jaspard-Vinassa, Beatrice; Bats, Marie-Lise; Sewduth, Raj N.; Franzl, Nathalie; Peghaire, Claire; Jeanningros, Sylvie; Moreau, Catherine; Roux, Etienne; Larrieu-Lahargue, Frederic; Dufourcq, Pascale; Couffinhal, Thierry; Duplàa, Cecile

    2016-01-01

    Angiogenesis involves the coordinated growth and migration of endothelial cells (ECs) toward a proangiogenic signal. The Wnt planar cell polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl-associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization for oriented cell migration. Here we report that Kif26b—a kinesin—and Daam1 cooperatively regulate initiation of EC sprouting and directional migration via MT reorganization. First, we find that Kif26b is recruited within the Dvl3/Daam1 complex. Using a three-dimensional in vitro angiogenesis assay, we show that Kif26b and Daam1 depletion impairs tip cell polarization and destabilizes extended vascular processes. Kif26b depletion specifically alters EC directional migration and mislocalized MT organizing center (MTOC)/Golgi and myosin IIB cell rear enrichment. Therefore the cell fails to establish a proper front–rear polarity. Of interest, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we show that Kif26b functions in MT stabilization, which is indispensable for asymmetrical cell structure reorganization. These data demonstrate that Kif26b, together with Dvl3/Daam1, initiates cell polarity through the control of PCP signaling pathway–dependent activation. PMID:26792835

  19. Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells.

    PubMed

    Recouvreux, Pierre; Sokolowski, Thomas R; Grammoustianou, Aristea; ten Wolde, Pieter Rein; Dogterom, Marileen

    2016-02-16

    Cell polarity refers to a functional spatial organization of proteins that is crucial for the control of essential cellular processes such as growth and division. To establish polarity, cells rely on elaborate regulation networks that control the distribution of proteins at the cell membrane. In fission yeast cells, a microtubule-dependent network has been identified that polarizes the distribution of signaling proteins that restricts growth to cell ends and targets the cytokinetic machinery to the middle of the cell. Although many molecular components have been shown to play a role in this network, it remains unknown which molecular functionalities are minimally required to establish a polarized protein distribution in this system. Here we show that a membrane-binding protein fragment, which distributes homogeneously in wild-type fission yeast cells, can be made to concentrate at cell ends by attaching it to a cytoplasmic microtubule end-binding protein. This concentration results in a polarized pattern of chimera proteins with a spatial extension that is very reminiscent of natural polarity patterns in fission yeast. However, chimera levels fluctuate in response to microtubule dynamics, and disruption of microtubules leads to disappearance of the pattern. Numerical simulations confirm that the combined functionality of membrane anchoring and microtubule tip affinity is in principle sufficient to create polarized patterns. Our chimera protein may thus represent a simple molecular functionality that is able to polarize the membrane, onto which additional layers of molecular complexity may be built to provide the temporal robustness that is typical of natural polarity patterns.

  20. Tissue growth and tumorigenesis in Drosophila: cell polarity and the Hippo pathway.

    PubMed

    Richardson, Helena E; Portela, Marta

    2017-03-28

    Cell polarity regulation is critical for defining membrane domains required for the establishment and maintenance of the apical-basal axis in epithelial cells (apico-basal polarity), asymmetric cell divisions, planar organization of tissues (planar cell polarity), and the formation of the front-rear axis in cell migration (front-rear polarity). In the vinegar fly, Drosophila melanogaster, cell polarity regulators also interact with the Hippo tissue growth control signaling pathway. In this review we survey the recent Drosophila literature linking cell polarity regulators with the Hippo pathway in epithelial tissue growth, neural stem cell asymmetric divisions and in cell migration in physiological and tumorigenic settings.

  1. Slit and Robo control cardiac cell polarity and morphogenesis.

    PubMed

    Qian, Li; Liu, Jiandong; Bodmer, Rolf

    2005-12-20

    Basic aspects of heart morphogenesis involving migration, cell polarization, tissue alignment, and lumen formation may be conserved between Drosophila and humans, but little is known about the mechanisms that orchestrate the assembly of the heart tube in either organism. The extracellular-matrix molecule Slit and its Robo-family receptors are conserved regulators of axonal guidance. Here, we report a novel role of the Drosophila slit, robo, and robo2 genes in heart morphogenesis. Slit and Robo proteins specifically accumulate at the dorsal midline between the bilateral myocardial progenitors forming a linear tube. Manipulation of Slit localization or its overexpression causes disruption in heart tube alignment and assembly, and slit-deficient hearts show disruptions in cell-polarity marker localization within the myocardium. Similar phenotypes are observed when Robo and Robo2 are manipulated. Rescue experiments suggest that Slit is secreted from the myocardial progenitors and that Robo and Robo2 act in myocardial and pericardial cells, respectively. Genetic interactions suggest a cardiac morphogenesis network involving Slit/Robo, cell-polarity proteins, and other membrane-associated proteins. We conclude that Slit and Robo proteins contribute significantly to Drosophila heart morphogenesis by guiding heart cell alignment and adhesion and/or by inhibiting cell mixing between the bilateral compartments of heart cell progenitors and ensuring proper polarity of the myocardial epithelium.

  2. Qualification of gridding process for a Polarization Sensitive Reflector (PSR)

    NASA Astrophysics Data System (ADS)

    Leitner, R.; Nathrath, N.; Schaefer, W.

    1986-08-01

    A polarization sensitive satellite reflector configuration for frequency reuse was developed. It consists of two Kevlar fiber sandwich shells oriented one behind the other and joined along the rim by a Kevlar fiber support ring. For electrical separation of the two systems, the reflector shell surfaces are covered with conductive strip grids which are oriented perpendicular with respect to each other. The gridding process allows direct application of the conductive strips on the prefabricated Kevlar sandwich dishes. Thermal cycling tests show that Tedlar is the most suitable polymeric film to cover the Kevlar surface.

  3. High voltage processing of the SLC polarized electron gun

    SciTech Connect

    Saez, P.; Clendenin, J.; Garden, C.; Hoyt, E.; Klaisner, L.; Prescott, C.; Schultz, D.; Tang, H.

    1993-04-01

    The SLC polarized electron gun operates at 120 kV with very low dark current to maintain the ultra high vacuum (UHV). This strict requirement protects the extremely sensitive photocathode from contaminants caused by high voltage (HV) activity. Thorough HV processing is thus required x-ray sensitive photographic film, a nanoammeter in series with gun power supply, a radiation meter, a sensitive residual gas analyzer and surface x-ray spectrometry were used to study areas in the gun where HV activity occurred. By reducing the electric field gradients, carefully preparing the HV surfaces and adhering to very strict clean assembly procedures, we found it possible to process the gun so as to reduce both the dark current at operating voltage and the probability of HV discharge. These HV preparation and processing techniques are described.

  4. Auxin Acts through MONOPTEROS to Regulate Plant Cell Polarity and Pattern Phyllotaxis.

    PubMed

    Bhatia, Neha; Bozorg, Behruz; Larsson, André; Ohno, Carolyn; Jönsson, Henrik; Heisler, Marcus G

    2016-12-05

    The periodic formation of plant organs such as leaves and flowers gives rise to intricate patterns that have fascinated biologists and mathematicians alike for hundreds of years [1]. The plant hormone auxin plays a central role in establishing these patterns by promoting organ formation at sites where it accumulates due to its polar, cell-to-cell transport [2-6]. Although experimental evidence as well as modeling suggest that feedback from auxin to its transport direction may help specify phyllotactic patterns [7-12], the nature of this feedback remains unclear [13]. Here we reveal that polarization of the auxin efflux carrier PIN-FORMED 1 (PIN1) is regulated by the auxin response transcription factor MONOPTEROS (MP) [14]. We find that in the shoot, cell polarity patterns follow MP expression, which in turn follows auxin distribution patterns. By perturbing MP activity both globally and locally, we show that localized MP activity is necessary for the generation of polarity convergence patterns and that localized MP expression is sufficient to instruct PIN1 polarity directions non-cell autonomously, toward MP-expressing cells. By expressing MP in the epidermis of mp mutants, we further show that although MP activity in a single-cell layer is sufficient to promote polarity convergence patterns, MP in sub-epidermal tissues helps anchor these polarity patterns to the underlying cells. Overall, our findings reveal a patterning module in plants that determines organ position by orienting transport of the hormone auxin toward cells with high levels of MP-mediated auxin signaling. We propose that this feedback process acts broadly to generate periodic plant architectures. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Cell polarity in fission yeast: a matter of confining, positioning, and switching growth zones.

    PubMed

    Huisman, Stephen M; Brunner, Damian

    2011-10-01

    The two key processes in growth polarisation are the generation of a confined region and the correct positioning of that region. Fission yeast has greatly contributed to the study of cell polarisation, particularly in the aspect of growth site positioning, which involves the interphase microtubule cytoskeleton. Here we review the mechanisms of growth polarity in vegetatively growing fission yeast cells. These seemingly simple cells show astonishingly complex growth polarity behaviour, including polarity switching and integrating multiple levels of control by the cell cycle machinery. We aim to extract and highlight the underlying concepts and discuss these in context of current understanding; showing how relevant proteins are networked to integrate the various machineries. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Processing TOVS Polar Pathfinder data using the distributed batch controller

    NASA Astrophysics Data System (ADS)

    Duff, James; Salem, Kenneth M.; Schweiger, Axel; Livny, Miron

    1997-09-01

    The distributed batch controller (DBC) supports scientific batch data processing. Batch jobs are distributed by the DBC over a collection of computing resources. Since these resources may be widely scattered the DBC is well suited for collaborative research efforts whose resources may not be centrally located. The DBC provides its users with centralized monitoring and control of distributed batch jobs. Version 1 of the DBC is currently being used by the TOVS Polar Pathfinder project to generate Arctic atmospheric temperature and humidity profiles. Profile generating jobs are distributed and executed by the DBC on workstation clusters located at several sites across the US. This paper describes the data processing requirements of the TOVS Polar Pathfinder project, and how the DBC is being used to meet them. It also describes Version 2 of the DBC. DBC V2 is implemented in Java, and utilizes a number of advanced Java features such as threads and remote method invocation. It incorporates a number of functional enhancements. These include a flexible mechanism supporting interoperation of the DBC with a wider variety of execution resources and an improved user interface.

  7. Mass balance processes on the north polar cap on Mars

    NASA Astrophysics Data System (ADS)

    Hvidberg, C. S.

    2003-04-01

    The permanent north polar cap is thought to consist of H2O ice with some dust and CO2 ice. The cap has formed over millions of years, and its topography at present is a result of geologic and climatic processes. A characteristic feature of the cap is a spiraling pattern of scarps and troughs organized around the pole. Horizontal or north-facing areas appear white, while the scarps expose dark layers. The alternating white polar ice and exposed layers suggest that the cap interacts with the atmosphere through deposition and sublimation processes and plays an active role in the current water cycle on Mars. The spiraling scarps and troughs are thought to be formed in a combination of sublimation, wind effects, deposition and ice flow. We use an ice sheet model to study these mechanisms, their effects and relative importance under the present climatic conditions. The characteristics suggest that the spiraling structure is a result of sublimation combined with wind effects. Ice flow alone would close the troughs within 100-1000 kyrs. Sublimation rates must exceed the flow rates and be in the order of cm/year in order to keep troughs open. We estimate the total amount of sublimation to be in the order of 10^11 to 10^12 kg per Martian year. The result indicates that the cap accounts for the observed annual input of water vapor to the northern hemisphere atmosphere.

  8. Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

    PubMed

    Noatynska, Anna; Tavernier, Nicolas; Gotta, Monica; Pintard, Lionel

    2013-08-07

    Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.

  9. Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

    PubMed Central

    Noatynska, Anna; Tavernier, Nicolas; Gotta, Monica; Pintard, Lionel

    2013-01-01

    Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression. PMID:23926048

  10. The variable polarity plasma arc welding process: Characteristics and performance

    NASA Technical Reports Server (NTRS)

    Hung, R. J.; Zhu, G. J.

    1991-01-01

    Significant advantages of the Variable Polarity Plasma Arc (VPPA) Welding Process include faster welding, fewer repairs, less joint preparation, reduced weldment distortion, and absence of porosity. The power distribution was analyzed for an argon plasma gas flow constituting the fluid in the VPPA Welding Process. The major heat loss at the torch nozzle is convective heat transfer; in the space between the outlet of the nozzle and the workpiece; radiative heat transfer; and in the keyhole in the workpiece, convective heat transfer. The power absorbed at the workpiece produces the molten puddle that solidifies into the weld bead. Crown and root widths, and crown and root heights of the weld bead are predicted. The basis is provided for an algorithm for automatic control of VPPA welding machine parameters to obtain desired weld bead dimensions.

  11. Sustained centrosome-cortical contact ensures robust polarization of the one-cell C. elegans embryo.

    PubMed

    Saturno, Dominique M; Castanzo, Dominic T; Williams, Margaret; Parikh, Devayu A; Jaeger, Eva C; Lyczak, Rebecca

    2017-02-15

    In C. elegans, the anterior-posterior axis is established at the one-cell stage when the embryo polarizes along its long axis. One model suggests that a cue from the centrosome triggers symmetry breaking and is then dispensable for further steps in the process. In the absence of the initial centrosome cue, a redundant mechanism, reliant on the centrosome's microtubules, can polarize the cell. Despite this model, data from multiple sources suggest that direct centrosome-contact with the cortex may play a role in ensuring robust polarization. Some of this past work includes analysis of pam-1 mutants, which lack a functional puromycin-sensitive aminopeptidase and have aberrant centrosome positioning and variable polarization defects. To better understand the role of centrosome dynamics in polarization, we looked in detail at centrosome behavior in relation to key polarity landmarks in pam-1 mutants as well as those lacking cortical flows. We provide evidence for a model in which sustained direct contact between the centrosome and the cortex acts to reinforce both the actomyosin and the microtubule-dependent pathways. This contact is necessary for polarization when flows are inhibited. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Competition for actin between two distinct F-actin networks defines a bistable switch for cell polarization.

    PubMed

    Lomakin, Alexis J; Lee, Kun-Chun; Han, Sangyoon J; Bui, Duyen A; Davidson, Michael; Mogilner, Alex; Danuser, Gaudenz

    2015-11-01

    Symmetry-breaking polarization enables functional plasticity of cells and tissues and is yet not well understood. Here we show that epithelial cells, hard-wired to maintain a static morphology and to preserve tissue organization, can spontaneously switch to a migratory polarized phenotype after relaxation of the actomyosin cytoskeleton. We find that myosin II engages actin in the formation of cortical actomyosin bundles and thus makes it unavailable for deployment in the process of dendritic growth normally driving cell motility. Under low-contractility regimes, epithelial cells polarize in a front-back manner owing to the emergence of actin retrograde flows powered by dendritic polymerization of actin. Coupled to cell movement, the flows transport myosin II from the front to the back of the cell, where the motor locally 'locks' actin in contractile bundles. This polarization mechanism could be employed by embryonic and cancer epithelial cells in microenvironments where high-contractility-driven cell motion is inefficient.

  13. EBV BMRF-2 facilitates cell-to-cell spread of virus within polarized oral epithelial cells

    PubMed Central

    Xiao, Jianqiao; Palefsky, Joel M.; Herrera, Rossana; Berline, Jennifer; Tugizov, Sharof M.

    2009-01-01

    We previously reported that the Epstein-Barr virus (EBV) BMRF-2 protein plays an important role in EBV infection of polarized oral epithelial cells by interacting with β1 and αv family integrins. Here we show that infection of polarized oral epithelial cells with B27-BMRF-2low recombinant virus, expressing a low level of BMRF-2, resulted in significantly smaller plaques compared with infection by parental B95-8 virus. BMRF-2 localized in the trans-Golgi network (TGN) and basolateral sorting vesicles and was transported to the basolateral membranes of polarized epithelial cells. Mutation of the tyrosine- and dileucine-containing basolateral sorting signal, YLLV, in the cytoplasmic domain of BMRF-2 led to the failure of its accumulation in the TGN and its basolateral transport. These data show that BMRF-2 may play an important role in promoting the spread of EBV progeny virions through lateral membranes of oral epithelial cells. PMID:19394065

  14. Spectral induced polarization for monitoring electrokinetic remediation processes

    NASA Astrophysics Data System (ADS)

    Masi, Matteo; Losito, Gabriella

    2015-12-01

    Electrokinetic remediation is an emerging technology for extracting heavy metals from contaminated soils and sediments. This method uses a direct or alternating electric field to induce the transport of contaminants toward the electrodes. The electric field also produces pH variations, sorption/desorption and precipitation/dissolution of species in the porous medium during remediation. Since heavy metal mobility is pH-dependent, the accurate control of pH inside the material is required in order to enhance the removal efficiency. The common approach for monitoring the remediation process both in laboratory and in the field is the chemical analysis of samples collected from discrete locations. The purpose of this study is the evaluation of Spectral Induced Polarization as an alternative method for monitoring geochemical changes in the contaminated mass during remediation. The advantage of this technique applied to field-scale is to offer higher resolution mapping of the remediation site and lower cost compared to the conventional sampling procedure. We carried out laboratory-scale electrokinetic remediation experiments on fine-grained marine sediments contaminated by heavy metal and we made Spectral Induced Polarization measurements before and after each treatment. Measurements were done in the frequency range 10- 3-103 Hz. By the deconvolution of the spectra using the Debye Decomposition method we obtained the mean relaxation time and total chargeability. The main finding of this work is that a linear relationship exists between the local total chargeability and pH, with good agreement. The observed behaviour of chargeability is interpreted as a direct consequence of the alteration of the zeta potential of the sediment particles due to pH changes. Such relationship has a significant value for the interpretation of induced polarization data, allowing the use of this technique for monitoring electrokinetic remediation at field-scale.

  15. When it is hard to get to with genetics--planar cell polarity under a chemical scalpel.

    PubMed

    Zou, Yimin

    2011-11-23

    Planar cell polarity (PCP) has been under genetic dissection for decades. More and more fundamental developmental processes have been found relying on PCP signaling. However, mechanisms of how PCP signaling generates asymmetry is still unknown. A recent paper in Chemistry & Biology (Sundberg et al., 2011) represents the efforts to decipher the intracellular code of polarity signaling.

  16. Polarity and asymmetric cell division in the control of lymphocyte fate decisions and function.

    PubMed

    Yassin, Mohammed; Russell, Sarah M

    2016-04-01

    Polarity is important in several lymphocyte processes including lymphocyte migration, formation of the immunological synapse, and asymmetric cell division (ACD). While lymphocyte migration and immunological synapse formation are relatively well understood, the role of lymphocyte ACD is less clear. Recent advances in measuring polarity enable more robust analyses of asymmetric cell division. Use of these new methods has produced crucial quantification of ACD at precise phases of lymphocyte development and activation. These developments are leading to a better understanding of the drivers of fate choice during lymphocyte activation and provide a context within which to explain the effects of ACD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Functional modelling of planar cell polarity: an approach for identifying molecular function

    PubMed Central

    2013-01-01

    Background Cells in some tissues acquire a polarisation in the plane of the tissue in addition to apical-basal polarity. This polarisation is commonly known as planar cell polarity and has been found to be important in developmental processes, as planar polarity is required to define the in-plane tissue coordinate system at the cellular level. Results We have built an in-silico functional model of cellular polarisation that includes cellular asymmetry, cell-cell signalling and a response to a global cue. The model has been validated and parameterised against domineering non-autonomous wing hair phenotypes in Drosophila. Conclusions We have carried out a systematic comparison of in-silico polarity phenotypes with patterns observed in vivo under different genetic manipulations in the wing. This has allowed us to classify the specific functional roles of proteins involved in generating cell polarity, providing new hypotheses about their specific functions, in particular for Pk and Dsh. The predictions from the model allow direct assignment of functional roles of genes from genetic mosaic analysis of Drosophila wings. PMID:23672397

  18. Polarized Growth Controls Cell Shape and Bipolar Bud Site Selection in Saccharomyces cerevisiae

    PubMed Central

    Sheu, Yi-Jun; Barral, Yves; Snyder, Michael

    2000-01-01

    We examined the relationship between polarized growth and division site selection, two fundamental processes important for proper development of eukaryotes. Diploid Saccharomyces cerevisiae cells exhibit an ellipsoidal shape and a specific division pattern (a bipolar budding pattern). We found that the polarity genes SPA2, PEA2, BUD6, and BNI1 participate in a crucial step of bud morphogenesis, apical growth. Deleting these genes results in round cells and diminishes bud elongation in mutants that exhibit pronounced apical growth. Examination of distribution of the polarized secretion marker Sec4 demonstrates that spa2Δ, pea2Δ, bud6Δ, and bni1Δ mutants fail to concentrate Sec4 at the bud tip during apical growth and at the division site during repolarization just prior to cytokinesis. Moreover, cell surface expansion is not confined to the distal tip of the bud in these mutants. In addition, we found that the p21-activated kinase homologue Ste20 is also important for both apical growth and bipolar bud site selection. We further examined how the duration of polarized growth affects bipolar bud site selection by using mutations in cell cycle regulators that control the timing of growth phases. The grr1Δ mutation enhances apical growth by stabilizing G1 cyclins and increases the distal-pole budding in diploids. Prolonging polarized growth phases by disrupting the G2/M cyclin gene CLB2 enhances the accuracy of bud site selection in wild-type, spa2Δ, and ste20Δ cells, whereas shortening the polarized growth phases by deleting SWE1 decreases the fidelity of bipolar budding. This study reports the identification of components required for apical growth and demonstrates the critical role of polarized growth in bipolar bud site selection. We propose that apical growth and repolarization at the site of cytokinesis are crucial for establishing spatial cues used by diploid yeast cells to position division planes. PMID:10866679

  19. Dermoscopic features of basal cell carcinomas: differences in appearance under non-polarized and polarized light.

    PubMed

    Liebman, Tracey N; Jaimes-Lopez, Natalia; Balagula, Yevgeniy; Rabinovitz, Harold S; Wang, Steven Q; Dusza, Stephen W; Marghoob, Ashfaq A

    2012-03-01

    Basal cell carcinomas (BCCs) can be diagnosed using different dermoscopic modalities. To evaluate dermoscopic features of BCCs using nonpolarized and polarized dermoscopy to highlight similarities and differences between dermoscopic modalities. Retrospective study of 149 BCCs under nonpolarized dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy (PNCD). Images were evaluated for a range of dermoscopic colors, structures, and vessels. Features were compared according to histopathologic subtype. The most common dermoscopic structures in BCCs across all modalities included globules (50.3-51.0%), dots (49.7-50.3%), white structureless areas (63.1-74.5%), structureless gray-brown areas (24.2-24.8%), and ulcerations (28.2%). The most frequently observed vasculature included arborizing vessels (18.8-38.3%), short fine telangiectasias (SFTs) (73.8-82.6%), and vascular blush (41.6-83.2%). Structures with higher levels of agreement across modalities included pigmented structures and ulcerations. Lower levels of agreement existed between contact and noncontact modalities for certain vascular features. White shiny structures, which include shiny white lines (chrysalis and crystalline structures) (0-69.1%), shiny white areas (0-25.5%), and rosettes (0-11.4%), exhibited no agreement between NPD and polarized modalities. This study highlights differences in dermoscopic features of BCCs under three dermoscopic modalities. Shiny white lines (chrysalis and crystalline structures) and shiny white areas may be used as additional criteria to diagnose BCCs. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  20. Vangl1 and Vangl2: planar cell polarity components with a developing role in cancer

    PubMed Central

    Hatakeyama, Jason; Wald, Jessica H; Printsev, Ignat; Ho, Hsin-Yi Henry; Carraway, Kermit L

    2015-01-01

    Cancers commonly reactivate embryonic developmental pathways to promote the aggressive behavior of their cells, resulting in metastasis and poor patient outcome. While developmental pathways such as canonical Wnt signaling and epithelial-to-mesenchymal transition have received much attention, our understanding of the role of the planar cell polarity (PCP) pathway in tumor progression remains rudimentary. Protein components of PCP, including a subset that overlaps with the canonical Wnt pathway, partition in polarized epithelial cells along the planar axis and are required for the establishment and maintenance of lateral epithelial polarity. Significant insight into PCP regulation of developmental and cellular processes has come from analysis of the functions of the core PCP scaffolding proteins Vangl1 and Vangl2. In particular, studies on zebrafish and with Looptail (Lp) mice, which harbor point mutations in Vangl2 that alter its trafficking and localization, point to roles for the PCP pathway in maintaining cell polarization along both the apical–basal and planar axes as well as in collective cell motility and invasiveness. Recent findings have suggested that the Vangls can promote similar processes in tumor cells. Initial data-mining efforts suggest that VANGL1 and VANGL2 are dysregulated in human cancers, and estrogen receptor (ER)-positive breast cancer patients whose tumors exhibit elevated VANGL1 expression suffer from shortened overall survival. Overall, evidence is beginning to accumulate that the heightened cellular motility and invasiveness associated with PCP reactivation may contribute to the malignancy of some cancer subtypes. PMID:24981109

  1. Regulation of bacterial cell polarity by small GTPases.

    PubMed

    Keilberg, Daniela; Søgaard-Andersen, Lotte

    2014-04-01

    Bacteria are polarized with many proteins localizing dynamically to specific subcellular sites. Two GTPase families have important functions in the regulation of bacterial cell polarity, FlhF homologues and small GTPases of the Ras superfamily. The latter consist of only a G domain and are widespread in bacteria. The rod-shaped Myxococcus xanthus cells have two motility systems, one for gliding and one that depends on type IV pili. The function of both systems hinges on proteins that localize asymmetrically to the cell poles. During cellular reversals, these asymmetrically localized proteins are released from their respective poles and then bind to the opposite pole, resulting in an inversion of cell polarity. Here, we review genetic, cell biological, and biochemical analyses that identified two modules containing small Ras-like GTPases that regulate the dynamic polarity of motility proteins. The GTPase SofG interacts directly with the bactofilin cytoskeletal protein BacP to ensure polar localization of type IV pili proteins. In the second module, the small GTPase MglA, its cognate GTPase activating protein (GAP) MglB, and the response regulator RomR localize asymmetrically to the poles and sort dynamically localized motility proteins to the poles. During reversals, MglA, MglB, and RomR switch poles, in that way inducing the relocation of dynamically localized motility proteins. Structural analyses have demonstrated that MglB has a Roadblock/LC7 fold, the central β2 strand in MglA undergoes an unusual screw-type movement upon GTP binding, MglA contains an intrinsic Arg finger required for GTP hydrolysis, and MglA and MglB form an unusual G protein/GAP complex with a 1:2 stoichiometry.

  2. The Accretion Process in Extremely High Magnetic Field Polars

    NASA Astrophysics Data System (ADS)

    Vogel, Justus

    2009-10-01

    We propose a triggered observation of one of the highest magnetic field polars known which escaped XMM-Newton so far. Utilizing the broad spectral range covered by XMM-Newton including the OM, we will simultaneously determine the energy content of the three cooling channels of the post-shock accretion plasma: cyclotron radiation in the UV, plasma radiation in hard X-rays and re-processed radiation in soft X-rays. We will confront our observations with state-of-art models and study quantitatively the energy balance of the cooling plasma as a function of white dwarf mass, accretion rate and magnetic field strength. Our targets, all with magnetic fields in excess of 100 MG give access to a rather unexplored parameter regime.

  3. The accretion process in AR UMa, an extremely magnetized polar

    NASA Astrophysics Data System (ADS)

    Scipione, Valentina

    2012-10-01

    We propose a triggered observation of the highest magnetized polar, AR UMa. Our target with a magnetic field of about 230 MG gives access to an unexplored parameter regime. It escaped XMM-Newton so far due to extended low states. Utilizing the broad spectral range covered by XMM-Newton including the OM, we will simultaneously determine the energy content of the three cooling channels of the post-shock accretion plasma: cyclotron radiation in the UV, plasma radiation in hard X-rays and re-processed radiation in soft X-rays. We will confront our observations with state-of-art models and study quantitatively the energy balance of the cooling plasma as a function of the accretion rate and the magnetic field strength.

  4. Differential trafficking of transforming growth factor-beta receptors and ligand in polarized epithelial cells.

    PubMed

    Murphy, S J; Doré, J J E; Edens, M; Coffey, R J; Barnard, J A; Mitchell, H; Wilkes, M; Leof, E B

    2004-06-01

    Epithelial cells in vivo form tight cell-cell associations that spatially separate distinct apical and basolateral domains. These domains provide discrete cellular processes essential for proper tissue and organ development. Using confocal imaging and selective plasma membrane domain activation, the type I and type II transforming growth factor-beta (TGFbeta) receptors were found to be localized specifically at the basolateral surfaces of polarized Madin-Darby canine kidney (MDCK) cells. Receptors concentrated predominantly at the lateral sites of cell-cell contact, adjacent to the gap junctional complex. Cytoplasmic domain truncations for each receptor resulted in the loss of specific lateral domain targeting and dispersion to both the apical and basal domains. Whereas receptors concentrate basolaterally in regions of direct cell-cell contact in nonpolarized MDCK cell monolayers, receptor staining was absent from areas of noncell contact. In contrast to the defined basolateral polarity observed for the TGFbeta receptor complex, TGFbeta ligand secretion was found to be from the apical surfaces. Confocal imaging of MDCK cells with an antibody to TGFbeta1 confirmed a predominant apical localization, with a stark absence at the basal membrane. These findings indicate that cell adhesion regulates the localization of TGFbeta receptors in polarized epithelial cultures and that the response to TGFbeta is dependent upon the spatial distribution and secretion of TGFbeta receptors and ligand, respectively.

  5. Noise filtering tradeoffs in spatial gradient sensing and cell polarization response

    PubMed Central

    2011-01-01

    Background Cells sense chemical spatial gradients and respond by polarizing internal components. This process can be disrupted by gradient noise caused by fluctuations in chemical concentration. Results We investigated how external gradient noise affects spatial sensing and response focusing on noise-filtering and the resultant tradeoffs. First, using a coarse-grained mathematical model of gradient-sensing and cell polarity, we characterized three negative consequences of noise: Inhibition of the extent of polarization, degradation of directional accuracy, and production of a noisy output polarization. Next, we explored filtering strategies and discovered that a combination of positive feedback, multiple signaling stages, and time-averaging produced good results. There was an important tradeoff, however, because filtering resulted in slower polarization. Simulations demonstrated that a two-stage filter-amplifier resulted in a balanced outcome. Then, we analyzed the effect of noise on a mechanistic model of yeast cell polarization in response to gradients of mating pheromone. This analysis showed that yeast cells likely also combine the above three filtering mechanisms into a filter-amplifier structure to achieve impressive spatial-noise tolerance, but with the consequence of a slow response time. Further investigation of the amplifier architecture revealed two positive feedback loops, a fast inner and a slow outer, both of which contributed to noise-tolerant polarization. This model also made specific predictions about how orientation performance depended upon the ratio between the gradient slope (signal) and the noise variance. To test these predictions, we performed microfluidics experiments measuring the ability of yeast cells to orient to shallow gradients of mating pheromone. The results of these experiments agreed well with the modeling predictions, demonstrating that yeast cells can sense gradients shallower than 0.1% μm-1, approximately a single receptor

  6. A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues.

    PubMed

    Parsons, Linda M; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

    2017-08-07

    In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 (SIK2 and 3) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development. Copyright © 2017 Parsons et al.

  7. Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells

    SciTech Connect

    Lee, Seung-Min; Attieh, Zouhair K.; Son, Hee Sook; Chen, Huijun; Bacouri-Haidar, Mhenia; Vulpe, Chris D.

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in non-polarized cells. Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in iron deficient and polarized cells. Black-Right-Pointing-Pointer Hephaestin with apical iron moves near to basolateral membrane of polarized cells. Black-Right-Pointing-Pointer Peri-basolateral location of hephaestin is accessible to the extracellular space. Black-Right-Pointing-Pointer Hephaestin is involved in iron mobilization from the intestine to circulation. -- Abstract: While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO{sub 4}) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a

  8. Parahydrogen-induced polarization in heterogeneous catalytic processes.

    PubMed

    Kovtunov, Kirill V; Zhivonitko, Vladimir V; Skovpin, Ivan V; Barskiy, Danila A; Koptyug, Igor V

    2013-01-01

    Parahydrogen-induced polarization of nuclear spins provides enhancements of NMR signals for various nuclei of up to four to five orders of magnitude in magnetic fields of modern NMR spectrometers and even higher enhancements in low and ultra-low magnetic fields. It is based on the use of parahydrogen in catalytic hydrogenation reactions which, upon pairwise addition of the two H atoms of parahydrogen, can strongly enhance the NMR signals of reaction intermediates and products in solution. A recent advance in this field is the demonstration that PHIP can be observed not only in homogeneous hydrogenations but also in heterogeneous catalytic reactions. The use of heterogeneous catalysts for generating PHIP provides a number of significant advantages over the homogeneous processes, including the possibility to produce hyperpolarized gases, better control over the hydrogenation process, and the ease of separation of hyperpolarized fluids from the catalyst. The latter advantage is of paramount importance in light of the recent tendency toward utilization of hyperpolarized substances in in vivo spectroscopic and imaging applications of NMR. In addition, PHIP demonstrates the potential to become a useful tool for studying mechanisms of heterogeneous catalytic processes and for in situ studies of operating catalytic reactors. Here, the known examples of PHIP observations in heterogeneous reactions over immobilized transition metal complexes, supported metals, and some other types of heterogeneous catalysts are discussed and the applications of the technique for hypersensitive NMR imaging studies are presented.

  9. Cell-Substrate Interactions Feedback to Direct Cell Migration along or against Morphological Polarization

    PubMed Central

    Kumar, Girish; Ho, Chia-Chi; Co, Carlos C.

    2015-01-01

    In response to external stimuli, cells polarize morphologically into teardrop shapes prior to moving in the direction of their blunt leading edge through lamellipodia extension and retraction of the rear tip. This textbook description of cell migration implies that the initial polarization sets the direction of cell migration. Using microfabrication techniques to control cell morphologies and the direction of migration without gradients, we demonstrate that after polarization, lamelipodia extension and attachment can feedback to change and even reverse the initial morphological polarization. Cells do indeed migrate faster in the direction of their morphologically polarization. However, feedback from subsequent lamellipodia extension and attachment can be so powerful as to induce cells to reverse and migrate against their initial polarization, albeit at a slower speed. Constitutively active mutants of RhoA show that RhoA stimulates cell motility when cells are guided either along or against their initial polarization. Cdc42 activation and inhibition, which results in loss of directional motility during chemotaxis, only reduces the speed of migration without altering the directionality of migration on the micropatterns. These results reveal significant differences between substrate directed cell migration and that induced by chemotactic gradients. PMID:26186588

  10. Coronavirus entry and release in polarized epithelial cells: a review.

    PubMed

    Cong, Yingying; Ren, Xiaofeng

    2014-09-01

    Most coronaviruses cause respiratory or intestinal infections in their animal or human host. Hence, their interaction with polarized epithelial cells plays a critical role in the onset and outcome of infection. In this paper, we review the knowledge regarding the entry and release of coronaviruses, with particular emphasis on the severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. As these viruses approach the epithelial surfaces from the apical side, it is not surprising that coronavirus cell receptors are exposed primarily on the apical domain of polarized epithelial cells. With respect to release, all possibilities appear to occur. Thus, most coronaviruses exit through the apical surface, several through the basolateral one, although the Middle East respiratory syndrome coronavirus appears to use both sides. These observations help us understand the local or systematic spread of the infection within its host as well as the spread of the virus within the host population.

  11. Regulation of cell polarity and RNA localization in vertebrate oocytes.

    PubMed

    Houston, Douglas W

    2013-01-01

    It has long been appreciated that the inheritance of maternal cytoplasmic determinants from different regions of the egg can lead to differential specification of blastomeres during cleavage. Localized RNAs are important determinants of cell fate in eggs and embryos but are also recognized as fundamental regulators of cell structure and function. This chapter summarizes recent molecular and genetic experiments regarding: (1) mechanisms that regulate polarity during different stages of vertebrate oogenesis, (2) pathways that localize presumptive protein and RNA determinants within the polarized oocyte and egg, and (3) how these determinants act in the embryo to determine the ultimate cell fates. Emphasis is placed on studies done in Xenopus, where extensive work has been done in these areas, and comparisons are drawn with fish and mammals. The prospects for future work using in vivo genome manipulation and other postgenomic approaches are also discussed. © 2013 Elsevier Inc. All rights reserved.

  12. Cell polarity, auxin transport, and cytoskeleton-mediated division planes: who comes first?

    PubMed

    Dhonukshe, Pankaj; Kleine-Vehn, Jürgen; Friml, Jiri

    2005-10-01

    In plants, cell polarity is an issue more recurring than in other systems, because plants, due to their adaptive and flexible development, often change cell polarity postembryonically according to intrinsic cues and demands of the environment. Recent findings on the directional movement of the plant signalling molecule auxin provide a unique connection between individual cell polarity and the establishment of polarity at the tissue, organ, and whole-plant levels. Decisions about the subcellular polar targeting of PIN auxin transport components determine the direction of auxin flow between cells and consequently mediate multiple developmental events. In addition, mutations or chemical interference with PIN-based auxin transport result in abnormal cell divisions. Thus, the complicated links between cell polarity establishment, auxin transport, cytoskeleton, and oriented cell divisions now begin to emerge. Here we review the available literature on the issues of cell polarity in both plants and animals to extend our understanding on the generation, maintenance, and transmission of cell polarity in plants.

  13. Collective chemotaxis requires contact-dependent cell polarity.

    PubMed

    Theveneau, Eric; Marchant, Lorena; Kuriyama, Sei; Gull, Mazhar; Moepps, Barbara; Parsons, Maddy; Mayor, Roberto

    2010-07-20

    Directional collective migration is now a widely recognized mode of migration during embryogenesis and cancer. However, how a cluster of cells responds to chemoattractants is not fully understood. Neural crest cells are among the most motile cells in the embryo, and their behavior has been likened to malignant invasion. Here, we show that neural crest cells are collectively attracted toward the chemokine Sdf1. While not involved in initially polarizing cells, Sdf1 directionally stabilizes cell protrusions promoted by cell contact. At this cell contact, N-cadherin inhibits protrusion and Rac1 activity and in turn promotes protrusions and activation of Rac1 at the free edge. These results show a role for N-cadherin during contact inhibition of locomotion, and they reveal a mechanism of chemoattraction likely to function during both embryogenesis and cancer metastasis, whereby attractants such as Sdf1 amplify and stabilize contact-dependent cell polarity, resulting in directional collective migration. (c) 2010 Elsevier Inc. All rights reserved.

  14. Satellite Cells in Muscular Dystrophy - Lost in Polarity.

    PubMed

    Chang, Natasha C; Chevalier, Fabien P; Rudnicki, Michael A

    2016-06-01

    Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem-cell divisions, and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review we highlight recent research advances in DMD and discuss the current state of treatment and, importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Satellite Cells in Muscular Dystrophy - Lost in Polarity

    PubMed Central

    Chang, Natasha C.; Chevalier, Fabien P.; Rudnicki, Michael A.

    2016-01-01

    Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem cell divisions and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility, but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review, we highlight recent research advances in DMD and discuss the current state of treatment and importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD. PMID:27161598

  16. Rho1-Wnd signaling regulates loss-of-cell polarity-induced cell invasion in Drosophila.

    PubMed

    Ma, X; Chen, Y; Zhang, S; Xu, W; Shao, Y; Yang, Y; Li, W; Li, M; Xue, L

    2016-02-18

    Both cell polarity and c-Jun N-terminal kinase (JNK) activity are essential to the maintenance of tissue homeostasis, and disruption of either is commonly seen in cancer progression. Despite the established connection between loss-of-cell polarity and JNK activation, much less is known about the molecular mechanism by which aberrant cell polarity induces JNK-mediated cell migration and tumor invasion. Here we show results from a genetic screen using an in vivo invasion model via knocking down cell polarity gene in Drosophila wing discs, and identify Rho1-Wnd signaling as an important molecular link that mediates loss-of-cell polarity-triggered JNK activation and cell invasion. We show that Wallenda (Wnd), a protein kinase of the mitogen-activated protein kinase kinase kinase family, by forming a complex with the GTPase Rho1, is both necessary and sufficient for Rho1-induced JNK-dependent cell invasion, MMP1 activation and epithelial-mesenchymal transition. Furthermore, Wnd promotes cell proliferation and tissue growth through wingless production when apoptosis is inhibited by p35. Finally, Wnd shows oncogenic cooperation with Ras(V12) to trigger tumor growth in eye discs and causes invasion into the ventral nerve cord. Together, our data not only provides a novel mechanistic insight on how cell polarity loss contributes to cell invasion, but also highlights the value of the Drosophila model system to explore human cancer biology.

  17. Polarization and orientation of retinal ganglion cells in vivo

    PubMed Central

    Zolessi, Flavio R; Poggi, Lucia; Wilkinson, Christopher J; Chien, Chi-Bin; Harris, William A

    2006-01-01

    In the absence of external cues, neurons in vitro polarize by using intrinsic mechanisms. For example, cultured hippocampal neurons extend arbitrarily oriented neurites and then one of these, usually the one nearest the centrosome, begins to grow more quickly than the others. This neurite becomes the axon as it accumulates molecular components of the apical junctional complex. All the other neurites become dendrites. It is unclear, however, whether neurons in vivo, which differentiate within a polarized epithelium, break symmetry by using similar intrinsic mechanisms. To investigate this, we use four-dimensional microscopy of developing retinal ganglion cells (RGCs) in live zebrafish embryos. We find that the situation is indeed very different in vivo, where axons emerge directly from uniformly polarized cells in the absence of other neurites. In vivo, moreover, components of the apical complex do not localize to the emerging axon, nor does the centrosome predict the site of axon emergence. Mosaic analysis in four dimensions, using mutants in which neuroepithelial polarity is disrupted, indicates that extrinsic factors such as access to the basal lamina are critical for normal axon emergence from RGCs in vivo. PMID:17147778

  18. Light scattering from Sickle Cell Hemoglobin: Polarized and Unpolarized

    NASA Astrophysics Data System (ADS)

    Chen, Kejing; Hantgan, Roy R.; Kim-Shapiro, Daniel B.

    1999-11-01

    Sickle cell polymers form due to aggregation of a mutant form of hemoglobin (HbS). The polymerization of HbS leads to microvascular occlusion characteristic of Sickle Cell Disease. A good understanding of HbS polymerization requires a way to quantify the degree of polymerization. As our calculations show, total intensity light scattering is not always linearly dependent on the amount of polymer. Polarized light scattering has been proposed as a more accurate way to measure polymer content. We use a new modulation method to measure all 16 Mueller Matrix elements, which completely describe how the Polarization State of light is altered upon scattering. Preliminary results of light scattering measurements from spheres and hemoglobin show that the instrument works properly. In future experiments, we will attempt to use polarized light scattering as an accurate measure of polymerization. In addition, Polarized light scattering may provide information on the higher order structure of sickle polymer bundles that has not been obtainable by other means.

  19. Planar Cell Polarity Signaling in Collective Cell Movements During Morphogenesis and Disease

    PubMed Central

    Muñoz-Soriano, Verónica; Belacortu, Yaiza; Paricio, Nuria

    2012-01-01

    Collective and directed cell movements are crucial for diverse developmental processes in the animal kingdom, but they are also involved in wound repair and disease. During these processes groups of cells are oriented within the tissue plane, which is referred to as planar cell polarity (PCP). This requires a tight regulation that is in part conducted by the PCP pathway. Although this pathway was initially characterized in flies, subsequent studies in vertebrates revealed a set of conserved core factors but also effector molecules and signal modulators, which build the fundamental PCP machinery. The PCP pathway in Drosophila regulates several developmental processes involving collective cell movements such as border cell migration during oogenesis, ommatidial rotation during eye development, and embryonic dorsal closure. During vertebrate embryogenesis, PCP signaling also controls collective and directed cell movements including convergent extension during gastrulation, neural tube closure, neural crest cell migration, or heart morphogenesis. Similarly, PCP signaling is linked to processes such as wound repair, and cancer invasion and metastasis in adults. As a consequence, disruption of PCP signaling leads to pathological conditions. In this review, we will summarize recent findings about the role of PCP signaling in collective cell movements in flies and vertebrates. In addition, we will focus on how studies in Drosophila have been relevant to our understanding of the PCP molecular machinery and will describe several developmental defects and human disorders in which PCP signaling is compromised. Therefore, new discoveries about the contribution of this pathway to collective cell movements could provide new potential diagnostic and therapeutic targets for these disorders. PMID:23730201

  20. Endocytic turnover of Rab8 controls cell polarization

    PubMed Central

    Vidal-Quadras, Maite; Holst, Mikkel R.; Larsson, Elin; Hachimi, Mariam; Yau, Wai-Lok; Peränen, Johan; Martín-Belmonte, Fernando

    2017-01-01

    ABSTRACT Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis. PMID:28137756

  1. Evolutionary adaptation after crippling cell polarization follows reproducible trajectories

    PubMed Central

    Laan, Liedewij; Koschwanez, John H; Murray, Andrew W

    2015-01-01

    Cells are organized by functional modules, which typically contain components whose removal severely compromises the module's function. Despite their importance, these components are not absolutely conserved between parts of the tree of life, suggesting that cells can evolve to perform the same biological functions with different proteins. We evolved Saccharomyces cerevisiae for 1000 generations without the important polarity gene BEM1. Initially the bem1∆ lineages rapidly increase in fitness and then slowly reach >90% of the fitness of their BEM1 ancestors at the end of the evolution. Sequencing their genomes and monitoring polarization reveals a common evolutionary trajectory, with a fixed sequence of adaptive mutations, each improving cell polarization by inactivating proteins. Our results show that organisms can be evolutionarily robust to physiologically destructive perturbations and suggest that recovery by gene inactivation can lead to rapid divergence in the parts list for cell biologically important functions. DOI: http://dx.doi.org/10.7554/eLife.09638.001 PMID:26426479

  2. Endocytic turnover of Rab8 controls cell polarization.

    PubMed

    Vidal-Quadras, Maite; Holst, Mikkel R; Francis, Monika K; Larsson, Elin; Hachimi, Mariam; Yau, Wai-Lok; Peränen, Johan; Martín-Belmonte, Fernando; Lundmark, Richard

    2017-03-15

    Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis.

  3. Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4{alpha}-induced epithelial polarization

    SciTech Connect

    Satohisa, Seiro; Chiba, Hideki . E-mail: hidchiba@sapmed.ac.jp; Osanai, Makoto; Ohno, Shigeo; Kojima, Takashi; Saito, Tsuyoshi; Sawada, Norimasa

    2005-10-15

    We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4{alpha} [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4{alpha} triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4{alpha}-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4{alpha} led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4{alpha} provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization.

  4. Rap1 integrates tissue polarity, lumen formation, and tumorigenicpotential in human breast epithelial cells

    SciTech Connect

    Itoh, Masahiko; Nelson, Celeste M.; Myers, Connie A.; Bissell,Mina J.

    2006-09-29

    Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Here we show that the small GTPase Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably higher than in S1 cells, their non-malignant counterparts. Expression of dominant-negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to formation of acinar structures with correct apico-basal polarity, and dramatically reduced tumor incidence despite the persistence of genomic abnormalities. The resulting acini contained prominent central lumina not observed when other reverting agents were used. Conversely, expression of dominant-active Rap1 in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness and tumorigenicity. Thus, Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing apical polarity during acinar morphogenesis, and increased activation inducing tumor formation and progression to malignancy.

  5. A possible mechanism for ezrin to establish epithelial cell polarity.

    PubMed

    Zhu, Lixin; Crothers, James; Zhou, Rihong; Forte, John G

    2010-08-01

    Ezrin is an important membrane/actin cytoskeleton linker protein, especially in epithelia. Ezrin has two important binding domains: an NH(2)-terminal region that binds to plasma membrane and a COOH-terminal region that binds to F-actin only after a conformational activation by phosphorylation at Thr567 of ezrin. The present experiments were undertaken to investigate the detailed cellular changes in the time course of expression of ezrin-T567 mutants (nonphosphorylatable T567A and permanent phospho-mimic T567D) in parietal cells and to assess ezrin distribution and its influence on the elaborate membrane recruitment processes of these cells. T567A mutant and wild-type (WT) ezrin were consistently localized to the apical plasma membrane, even with overexpression. On the other hand, T567D went first to apical membrane at early times and low expression levels, then accumulated mainly at the basal surface after 24 h. Overexpression of WT or T567A led to incorporation of internal membranes to apical vacuoles, while overexpression of T567D led to large incorporation of apical and intracellular membranes (including H-K-ATPase) to the basal surface. Differences in polar distribution of ezrin suggest a role for the linker protein in promoting formation and plasticity of membrane surface projections, forming the basis for a novel theory for ezrin as an organizer and regulator of membrane recruitment. A model simulating the cellular distribution of ezrin and its associated membrane- and F-actin-binding forms is given to predict redistributions observed with phosphorylation and mutant overexpression, and it can easily be modified as more specific information regarding binding constants and specific sites becomes available.

  6. Cell polarity determinants establish asymmetry in MEN signaling.

    PubMed

    Monje-Casas, Fernando; Amon, Angelika

    2009-01-01

    Components of the mitotic exit network (MEN), a signaling pathway that triggers exit from mitosis, localize to the spindle pole body (SPB) that migrates into the daughter cell during anaphase but are largely absent from the SPB that remains in the mother cell. Through the analysis of one of the determinants of this asymmetry, Bfa1, we find that the machinery responsible for establishing cell polarity and cytoplasmic microtubules collaborate to establish MEN asymmetry. In cells defective in the Cdc42 signaling pathway or the formin Bni1, Bfa1 localizes to both SPBs. The quantitative analysis of Bfa1 localization further shows that Bfa1 can associate with both SPBs in a transient and highly dynamic fashion, but the protein is stabilized on the SPB that migrates into the daughter cell during anaphase through microtubule-bud cortex interactions. Our results indicate that mother-daughter cell asymmetry determinants establish MEN signaling asymmetry through microtubule-bud cortex interactions.

  7. Myosin-X functions in polarized epithelial cells.

    PubMed

    Liu, Katy C; Jacobs, Damon T; Dunn, Brian D; Fanning, Alan S; Cheney, Richard E

    2012-05-01

    Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of filopodia and has critical functions in filopodia. Although Myo10 has been studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in vivo in many epithelia-rich tissues, such as kidney. In this study, we investigate the localization and functions of Myo10 in polarized epithelial cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch experiments demonstrate that, during junction assembly, green fluorescent protein-Myo10 localizes to lateral membrane cell-cell contacts and to filopodia-like structures imaged by total internal reflection fluorescence on the basal surface. Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to junctions, as well as a delay in tight junction barrier formation, as indicated by a delay in the development of peak transepithelial electrical resistance (TER). Although Myo10 knockdown cells eventually mature into monolayers with normal TER, these monolayers do exhibit increased paracellular permeability to fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit defects in lumen formation. Together these results reveal that Myo10 functions in polarized epithelial cells in junction formation, regulation of paracellular permeability, and epithelial morphogenesis.

  8. Cell-alignment patterns in the collective migration of cells with polarized adhesion

    NASA Astrophysics Data System (ADS)

    Matsushita, Katsuyoshi

    2017-03-01

    Dictyostelium discoideum (Dd) utilizes inhomogeneities in the distribution of cell-cell adhesion molecules on cell membranes for collective cell migration. A simple example of an inhomogeneity is a front-side (leading-edge) polarization in the distribution at the early streaming stage. Experiments have shown that the polarized cell-cell adhesion induces side-by-side contact between cells [Beug et al., Nature (London) 274, 445 (1978), 10.1038/274445a0]. This result is counterintuitive, as one would expect cells to align front to front in contact with each other on the basis of front-side polarization. In this work, we theoretically examine whether front-side polarization induces side-by-side contact in collective cell migration. We construct a model for expressing cells with this polarization based on the two-dimensional cellular Potts model. By a numerical simulation with this model, we find cell-cell alignment wherein cells form lateral arrays with side-by-side contacts as observed in the experiments.

  9. Minimal model for spontaneous cell polarization and edge activity in oscillating, rotating and migrating cells

    NASA Astrophysics Data System (ADS)

    Raynaud, Franck; Ambühl, Mark E.; Gabella, Chiara; Bornert, Alicia; Sbalzarini, Ivo F.; Meister, Jean-Jacques; Verkhovsky, Alexander B.

    2016-04-01

    How cells break symmetry and organize activity at their edges to move directionally is a fundamental question in cell biology. Physical models of cell motility commonly incorporate gradients of regulatory proteins and/or feedback from the motion itself to describe the polarization of this edge activity. These approaches, however, fail to explain cell behaviour before the onset of polarization. We use polarizing and moving fish epidermal cells as a model system to bridge the gap between cell behaviours before and after polarization. Our analysis suggests a novel and simple principle of self-organizing cell activity, in which local cell-edge dynamics depends on the distance from the cell centre, but not on the orientation with respect to the front-back axis. We validate this principle with a stochastic model that faithfully reproduces a range of cell-migration behaviours. Our findings indicate that spontaneous polarization, persistent motion and cell shape are emergent properties of the local cell-edge dynamics controlled by the distance from the cell centre.

  10. Cell polarity and neurogenesis in embryonic stem cell-derived neural rosettes.

    PubMed

    Banda, Erin; McKinsey, Anna; Germain, Noelle; Carter, James; Anderson, Nickesha Camille; Grabel, Laura

    2015-04-15

    Embryonic stem cells (ESCs) undergoing neural differentiation form radial arrays of neural stem cells, termed neural rosettes. These structures manifest many of the properties associated with embryonic and adult neurogenesis, including cell polarization, interkinetic nuclear migration (INM), and a gradient of neuronal differentiation. We now identify novel rosette structural features that serve to localize key regulators of neurogenesis. Cells within neural rosettes have specialized basal as well as apical surfaces, based on localization of the extracellular matrix receptor β1 integrin. Apical processes of cells in mature rosettes terminate at the lumen, where adherens junctions are apparent. Primary cilia are randomly distributed in immature rosettes and tightly associated with the neural stem cell's apical domain as rosettes mature. Components of two signaling pathways known to regulate neurogenesis in vivo and in rosettes, Hedgehog and Notch, are apically localized, with the Hedgehog effector Smoothened (Smo) associated with primary cilia and the Notch pathway γ-secretase subunit Presenilin 2 associated with the adherens junction. Increased neuron production upon treatment with the Notch inhibitor DAPT suggests a major role for Notch signaling in maintaining the neural stem cell state, as previously described. A less robust outcome was observed with manipulation of Hedgehog levels, though consistent with a role in neural stem cell survival or proliferation. Inhibition of both pathways resulted in an additive effect. These data support a model by which cells extending a process to the rosette lumen maintain neural stem cell identity whereas release from this association, either through asymmetric cell division or apical abscission, promotes neuronal differentiation.

  11. Polarized THG Microscopy Identifies Compositionally Different Lipid Droplets in Mammalian Cells

    PubMed Central

    Bautista, Godofredo; Pfisterer, Simon G.; Huttunen, Mikko J.; Ranjan, Sanjeev; Kanerva, Kristiina; Ikonen, Elina; Kauranen, Martti

    2014-01-01

    Cells store excess lipids as two major compounds, triacylglycerols (TAGs) and cholesteryl esters (CEs), inside lipid droplets (LDs). The degree of lipid ordering is considered to play a major role in the mobility and enzymatic processing of lipids in LDs. Here, we provide evidence that polarized third-harmonic generation (THG) microscopy distinguishes between native TAG- and CE-enriched LDs in cells due to the different ordering of the two lipid species. We first demonstrate that the responses from synthetic TAG- and CE-enriched LDs using THG microscopy with linear and circular polarizations differ according to their different intrinsic ordering. We then employ simulations to dissect how polarization effects influence the THG from an isotropic LD. Finally, we induce TAG- and CE-enriched LDs in murine macrophages and demonstrate that polarized THG responses increase in a nonlinear fashion with increasing CE/TAG ratio. This suggests that with an increasing CE content, there is a rather sharp transition toward increased LD ordering. Our results demonstrate that polarized THG microscopy enables label-free quantitative analysis of LD ordering and discriminates between compositionally different LDs in intact mammalian cells. PMID:25418291

  12. T Cell Migration in Three-dimensional Extracellular Matrix: Guidance by Polarity and Sensations

    PubMed Central

    Bröker, Eva-Bettina

    2000-01-01

    The locomotion of T lymphocytes within 3-D extracellular matrix (ECM) is a highly dynamic and flexible process following the principles of ameboid movement. Ameboid motility is characterized by a polarized yet simple cell shape allowing high speed, rapid directional oscillations, and low affinity interactions to the substrate that are coupled to a low degree of cytoskeletal organization lacking discrete focal contacts. At the onset of T cell migration, a default program, here described as migration-associated polarization, is initiated, resulting in the polar redistribution of cell surface receptors and cytoskeletal elements. Polarization involves protein cycling either to the leading edge (i.e. LFA-1, CD45RO, chemokine receptors, focal adhesion kinase), to a central polarizing compartment (MTOC, PKC, MARCKS), or into the uropod (CD44, CD43, ICAM- and –3, β1 integrins). The function of such compartment formation may be important in chemotactic response, scanning of encountered cells, and a flexible and adaptive interaction with the ECM itself. Due to the simple shape and a diffusely organized cytoskeleton, the interactions to the surrounding extracellular matrix are rapid and reversible and appear to allow a broad spectrum of molecular migration strategies. These range from (1) adhesive and haptokinetic following i.e. chemokine-induced motility across 2-D surfaces to (2) largely integrin-independent migration predominantly guided by shape change and morphological flexibility, as seen in 3-D type I collagen matrices. Their prominent capacity to rapidly adapt to a given structural environment coupled to contact guidance mechanisms set T cell locomotion apart from slow, focal contact-dependent and more adhesive migration strategies established by fibroblast-like cells and cell clusters. It is therefore likely that, within the tissues, besides chemotactic or haptotactic gradients, the preformed matrix structure has an important impact on T cell trafficking and

  13. A Distinct Pathway for Polar Exocytosis in Plant Cell Wall Formation1[OPEN

    PubMed Central

    Wang, Hao; Zhuang, Xiaohong; Wang, Xiangfeng; Law, Angus Ho Yin; Zhao, Teng; Du, Shengwang; Loy, Michael M.T.; Jiang, Liwen

    2016-01-01

    Post-Golgi protein sorting and trafficking to the plasma membrane (PM) is generally believed to occur via the trans-Golgi network (TGN). In this study using Nicotiana tabacum pectin methylesterase (NtPPME1) as a marker, we have identified a TGN-independent polar exocytosis pathway that mediates cell wall formation during cell expansion and cytokinesis. Confocal immunofluorescence and immunogold electron microscopy studies demonstrated that Golgi-derived secretory vesicles (GDSVs) labeled by NtPPME1-GFP are distinct from those organelles belonging to the conventional post-Golgi exocytosis pathway. In addition, pharmaceutical treatments, superresolution imaging, and dynamic studies suggest that NtPPME1 follows a polar exocytic process from Golgi-GDSV-PM/cell plate (CP), which is distinct from the conventional Golgi-TGN-PM/CP secretion pathway. Further studies show that ROP1 regulates this specific polar exocytic pathway. Taken together, we have demonstrated an alternative TGN-independent Golgi-to-PM polar exocytic route, which mediates secretion of NtPPME1 for cell wall formation during cell expansion and cytokinesis and is ROP1-dependent. PMID:27531442

  14. Incorporating metal into polarized 3He target cells

    NASA Astrophysics Data System (ADS)

    Katugampola, Sumudu K.; Matyas, Daniel J.; Wang, Yunxiao; Tobias, William A.; Nelyubin, Vladimir; Cates, Gordon D.

    2017-01-01

    An upcoming measurement at Jefferson Laboratory (JLab) of the electric form factor of the neutron will utilize a polarized 3He target at high luminosity. While polarized 3He targets at JLab have previously been made entirely of glass, we describe progress toward incorporating metal windows for the electron beam. Under the conditions of our targets, very few studies have been done on the spin-relaxation of nuclear-polarized 3He on metal surfaces. We have found good performance by using Oxygen Free High Conductivity (OFHC) copper substrates electroplated with gold. The glass-to-metal transitions within our test cells were based on Housekeeper seals. We have further established that Uranium glass (Canary glass) has excellent spin-relaxation properties, and can serve as a transition glass from Pyrex to Aluminosilicate glass (GE180). Another finding was that spin-relaxation properties were sensitive to the manner in which cells were annealed, an important issue because of constraints when annealing cells containing both metal and glass.

  15. Cytokinesis-Based Constraints on Polarized Cell Growth in Fission Yeast

    PubMed Central

    Bohnert, K. Adam; Gould, Kathleen L.

    2012-01-01

    The rod-shaped fission yeast Schizosaccharomyces pombe, which undergoes cycles of monopolar-to-bipolar tip growth, is an attractive organism for studying cell-cycle regulation of polarity establishment. While previous research has described factors mediating this process from interphase cell tips, we found that division site signaling also impacts the re-establishment of bipolar cell growth in the ensuing cell cycle. Complete loss or targeted disruption of the non-essential cytokinesis protein Fic1 at the division site, but not at interphase cell tips, resulted in many cells failing to grow at new ends created by cell division. This appeared due to faulty disassembly and abnormal persistence of the cell division machinery at new ends of fic1Δ cells. Moreover, additional mutants defective in the final stages of cytokinesis exhibited analogous growth polarity defects, supporting that robust completion of cell division contributes to new end-growth competency. To test this model, we genetically manipulated S. pombe cells to undergo new end take-off immediately after cell division. Intriguingly, such cells elongated constitutively at new ends unless cytokinesis was perturbed. Thus, cell division imposes constraints that partially override positive controls on growth. We posit that such constraints facilitate invasive fungal growth, as cytokinesis mutants displaying bipolar growth defects formed numerous pseudohyphae. Collectively, these data highlight a role for previous cell cycles in defining a cell's capacity to polarize at specific sites, and they additionally provide insight into how a unicellular yeast can transition into a quasi-multicellular state. PMID:23093943

  16. A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues

    PubMed Central

    Parsons, Linda M.; Grzeschik, Nicola A.; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M.; Richardson, Helena E.

    2017-01-01

    In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila “cell polarity” eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the “nutrient sensing” kinases Salt Inducible Kinase 2 and 3 (SIK2 and 3) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development. PMID:28611255

  17. N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli.

    PubMed

    Liu, Hong-Cui; Zheng, Min-Hua; Du, Yan-Ling; Wang, Li; Kuang, Fang; Qin, Hong-Yan; Zhang, Bing-Fang; Han, Hua

    2012-01-01

    Microglia participates in the regulation of many inflammation-related pathological processes in the central nervous system, but how microglial activation is regulated has not been fully understood. Here, by using a microglial cell line, we show that microglia, like other macrophages, are activated by inflammatory stimuli in a polarized manner. The LPS-polarized M1 microglia appeared to be unable to respond to a secondary IL4 stimulation, while IL4-polarized M2 microglia could respond to secondary LPS stimulation. We also show that Notch signaling is involved in microglial polarization. When Notch signaling was blocked, the M1 polarization was suppressed, while the M2 polarization was promoted. Withdraw of the Notch signal inhibitor did not permit M2 N9 cells to re-polarize to M1 upon LPS stimulation, suggesting that the effects of Notch blockade on microglial polarization could be "memorized" by cells. These results suggest complicated mechanisms including epigenetic programs in the regulation of macrophage polarization.

  18. Appearance of differentiated cells derived from polar body nuclei in the silkworm, Bombyx mori.

    PubMed

    Sakai, Hiroki; Yokoyama, Takeshi; Abe, Hiroaki; Fujii, Tsuguru; Suzuki, Masataka G

    2013-01-01

    In Bombyx mori, polar body nuclei are observed until 9 h after egg lying, however, the fate of polar body nuclei remains unclear. To examine the fate of polar body nuclei, we employed a mutation of serosal cell pigmentation, pink-eyed white egg (pe). The heterozygous pe/+ (pe) females produced black serosal cells in white eggs, while pe/pe females did not produce black serosal cells in white eggs. These results suggest that the appearance of black serosal cells in white eggs depends on the genotype (pe/+ (pe) ) of the mother. Because the polar body nuclei had + (pe) genes in the white eggs laid by a pe/+ (pe) female, polar body nuclei participate in development and differentiate into functional cell (serosal cells). Analyses of serosal cells pigmentation indicated that ~30% of the eggs contained polar-body-nucleus-derived cells. These results demonstrate that polar-body-nucleus-derived cells appeared at a high frequency under natural conditions. Approximately 80% of polar-body-nucleus-derived cells appeared near the anterior pole and the dorsal side, which is opposite to where embryogenesis occurs. The number of cells derived from the polar body nuclei was very low. Approximately 26% of these eggs contained only one black serosal cell. PCR-based analysis revealed that the polar-body-nucleus-derived cells disappeared in late embryonic stages (stage 25). Overall, polar-body-nuclei-derived cells were unlikely to contribute to embryos.

  19. Appearance of differentiated cells derived from polar body nuclei in the silkworm, Bombyx mori

    PubMed Central

    Sakai, Hiroki; Yokoyama, Takeshi; Abe, Hiroaki; Fujii, Tsuguru; Suzuki, Masataka G.

    2013-01-01

    In Bombyx mori, polar body nuclei are observed until 9 h after egg lying, however, the fate of polar body nuclei remains unclear. To examine the fate of polar body nuclei, we employed a mutation of serosal cell pigmentation, pink-eyed white egg (pe). The heterozygous pe/+pe females produced black serosal cells in white eggs, while pe/pe females did not produce black serosal cells in white eggs. These results suggest that the appearance of black serosal cells in white eggs depends on the genotype (pe/+pe) of the mother. Because the polar body nuclei had +pe genes in the white eggs laid by a pe/+pe female, polar body nuclei participate in development and differentiate into functional cell (serosal cells). Analyses of serosal cells pigmentation indicated that ~30% of the eggs contained polar-body-nucleus-derived cells. These results demonstrate that polar-body-nucleus-derived cells appeared at a high frequency under natural conditions. Approximately 80% of polar-body-nucleus-derived cells appeared near the anterior pole and the dorsal side, which is opposite to where embryogenesis occurs. The number of cells derived from the polar body nuclei was very low. Approximately 26% of these eggs contained only one black serosal cell. PCR-based analysis revealed that the polar-body-nucleus-derived cells disappeared in late embryonic stages (stage 25). Overall, polar-body-nuclei-derived cells were unlikely to contribute to embryos. PMID:24027530

  20. Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona.

    PubMed

    Veeman, Michael T; McDonald, Jocelyn A

    2016-01-01

    Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC) and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa.

  1. Polarization information processing and software system design for simultaneously imaging polarimetry

    NASA Astrophysics Data System (ADS)

    Wang, Yahui; Liu, Jing; Jin, Weiqi; Wen, Renjie

    2015-08-01

    Simultaneous imaging polarimetry can realize real-time polarization imaging of the dynamic scene, which has wide application prospect. This paper first briefly illustrates the design of the double separate Wollaston Prism simultaneous imaging polarimetry, and then emphases are put on the polarization information processing methods and software system design for the designed polarimetry. Polarization information processing methods consist of adaptive image segmentation, high-accuracy image registration, instrument matrix calibration. Morphological image processing was used for image segmentation by taking dilation of an image; The accuracy of image registration can reach 0.1 pixel based on the spatial and frequency domain cross-correlation; Instrument matrix calibration adopted four-point calibration method. The software system was implemented under Windows environment based on C++ programming language, which realized synchronous polarization images acquisition and preservation, image processing and polarization information extraction and display. Polarization data obtained with the designed polarimetry shows that: the polarization information processing methods and its software system effectively performs live realize polarization measurement of the four Stokes parameters of a scene. The polarization information processing methods effectively improved the polarization detection accuracy.

  2. Bazooka/PAR3 is dispensable for polarity in Drosophila follicular epithelial cells.

    PubMed

    Shahab, Jaffer; Tiwari, Manu D; Honemann-Capito, Mona; Krahn, Michael P; Wodarz, Andreas

    2015-03-13

    Apico-basal polarity is the defining characteristic of epithelial cells. In Drosophila, apical membrane identity is established and regulated through interactions between the highly conserved Par complex (Bazooka/Par3, atypical protein kinase C and Par6), and the Crumbs complex (Crumbs, Stardust and PATJ). It has been proposed that Bazooka operates at the top of a genetic hierarchy in the establishment and maintenance of apico-basal polarity. However, there is still ambiguity over the correct sequence of events and cross-talk with other pathways during this process. In this study, we reassess this issue by comparing the phenotypes of the commonly used baz(4) and baz(815-8) alleles with those of the so far uncharacterized baz(XR11) and baz(EH747) null alleles in different Drosophila epithelia. While all these baz alleles display identical phenotypes during embryonic epithelial development, we observe strong discrepancies in the severity and penetrance of polarity defects in the follicular epithelium: polarity is mostly normal in baz(EH747) and baz(XR11) while baz(4) and baz(815) (-8) show loss of polarity, severe multilayering and loss of epithelial integrity throughout the clones. Further analysis reveals that the chromosomes carrying the baz(4) and baz(815-8) alleles may contain additional mutations that enhance the true baz loss-of-function phenotype in the follicular epithelium. This study clearly shows that Baz is dispensable for the regulation of polarity in the follicular epithelium, and that the requirement for key regulators of cell polarity is highly dependent on developmental context and cell type.

  3. Cell division resets polarity and motility for the bacterium Myxococcus xanthus.

    PubMed

    Harvey, Cameron W; Madukoma, Chinedu S; Mahserejian, Shant; Alber, Mark S; Shrout, Joshua D

    2014-11-01

    Links between cell division and other cellular processes are poorly understood. It is difficult to simultaneously examine division and function in most cell types. Most of the research probing aspects of cell division has experimented with stationary or immobilized cells or distinctly asymmetrical cells. Here we took an alternative approach by examining cell division events within motile groups of cells growing on solid medium by time-lapse microscopy. A total of 558 cell divisions were identified among approximately 12,000 cells. We found an interconnection of division, motility, and polarity in the bacterium Myxococcus xanthus. For every division event, motile cells stop moving to divide. Progeny cells of binary fission subsequently move in opposing directions. This behavior involves M. xanthus Frz proteins that regulate M. xanthus motility reversals but is independent of type IV pilus "S motility." The inheritance of opposing polarity is correlated with the distribution of the G protein RomR within these dividing cells. The constriction at the point of division limits the intracellular distribution of RomR. Thus, the asymmetric distribution of RomR at the parent cell poles becomes mirrored at new poles initiated at the site of division.

  4. New findings in the mechanisms regulating polar growth in root hair cells

    PubMed Central

    2009-01-01

    Root hairs cells are highly polarized cellular structures resulting from tip growth of specific root epidermal cells. Root-hair morphogenesis involves many aspects regulating tip growth such as exocitosis, ion flux, calcium homeostasis, reactive oxygen species (ROS), and cytoskeleton. These cells are excellent models for studying polar growth and can be challenged with many extracellular factors affecting the pattern of growth named Nod factors, elicitors, hormones, etc. The general scenery is that the well described tip-high intracellular Ca2+ gradient plays a central role in regulating tip growth. On the other hand, ROS plays a key role in various processes, for example hypersensitive response, root hair development, hormone action, gravitropism and stress responses. However, ROS has recently emerged as a key player together with calcium in regulating polar growth, not only in root hair cells but also in pollen tubes, filamentous fungi and fucoid cells. Furthermore, Ca2+-permeable channel modulation by ROS has been demonstrated in Vicia faba guard cells and Arabidopsis root hairs. Recently, root hair cells were shown to experiment ROS, pH and calcium oscillations coupled to growth oscillation. These recent findings allow considering that root hair cells present a similar pattern of growth as described for pollen tubes. PMID:19568333

  5. New findings in the mechanisms regulating polar growth in root hair cells.

    PubMed

    Cárdenas, Luis

    2009-01-01

    Root hairs cells are highly polarized cellular structures resulting from tip growth of specific root epidermal cells. Root-hair morphogenesis involves many aspects regulating tip growth such as exocytosis, ion flux, calcium homeostasis, reactive oxygen species (ROS), and cytoskeleton. These cells are excellent models for studying polar growth and can be challenged with many extracellular factors affecting the pattern of growth named Nod factors, elicitors, hormones, etc. The general scenery is that the well described tip-high intracellular Ca(2+) gradient plays a central role in regulating tip growth. On the other hand, ROS plays a key role in various processes, for example hypersensitive response, root hair development, hormone action, gravitropism and stress responses. However, ROS has recently emerged as a key player together with calcium in regulating polar growth, not only in root hair cells but also in pollen tubes, filamentous fungi and fucoid cells. Furthermore, Ca(2+)-permeable channel modulation by ROS has been demonstrated in Vicia faba guard cells and Arabidopsis root hairs. Recently, root hair cells were shown to experiment ROS, pH and calcium oscillations coupled to growth oscillation. These recent findings allow considering that root hair cells present a similar pattern of growth as described for pollen tubes.

  6. Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

    PubMed

    Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

    2015-04-20

    During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs.

  7. Polar process and world climate /A brief overview/

    NASA Technical Reports Server (NTRS)

    Goody, R.

    1980-01-01

    A review is presented of events relating polar regions to the world climate, the mechanisms of sea ice and polar ice sheets, and of two theories of the Pleistocene Ice Ages. The sea ice which varies over time scales of one or two years and the polar ice sheets with time changes measured in tens or hundreds of thousands of years introduce two distinct time constants into global time changes; the yearly Arctic sea ice variations affect northern Europe and have some effect over the entire Northern Hemisphere; the ice-albedo coupling in the polar ice sheets is involved in major climatic events such as the Pleistocene ice ages. It is concluded that climate problems require a global approach including the atmosphere, the oceans, and the cryosphere.

  8. Studies of interactive plasma processes in the polar cusp

    NASA Technical Reports Server (NTRS)

    Waite, J. Hunter, Jr.

    1992-01-01

    Progress during the reporting period is presented. Several distinctly different areas of research are presently being pursued: (1) studies of the thermal structure of polar outflows; (2) Prognoz data analysis; and (3) Ulysses Jupiter encounter.

  9. An unconventional myosin required for cell polarization and chemotaxis.

    PubMed

    Breshears, Laura M; Wessels, Deborah; Soll, David R; Titus, Margaret A

    2010-04-13

    MyTH/FERM (myosin tail homology 4/band 4.1, ezrin, radixin, and moesin) myosins have roles in cellular adhesion, extension of actin-filled projections such as filopodia and stereocilia, and directional migration. The amoeba Dictyostelium discoideum expresses a simple complement of MyTH/FERM myosins, a class VII (M7) myosin required for cell-substrate adhesion and a unique myosin named MyoG. Mutants lacking MyoG exhibit a wide range of normal actin-based behaviors, including chemotaxis to folic acid, but have a striking defect in polarization and chemotaxis to cAMP. Although the myoG mutants respond to cAMP stimulation by increasing persistence and weakly increasing levels of cortical F-actin, they do not polarize; instead, they maintain a round shape and move slowly and randomly when exposed to a chemotactic gradient. The mutants also fail to activate and localize PI3K to the membrane closest to the source of chemoattractant. These data reveal a role for a MyTH/FERM myosin in mediating early chemotactic signaling and suggest that MyTH/FERM proteins have conserved roles in signaling and the generation of cell polarity.

  10. A biomechanical model for cell polarization and intercalation during Drosophila germband extension

    NASA Astrophysics Data System (ADS)

    Lan, Haihan; Wang, Qiming; Fernandez-Gonzalez, Rodrigo; Feng, James J.

    2015-10-01

    Germband extension during Drosophila development features the merging of cells along the dorsal-ventral (DV) axis and their separation along the anterior-posterior (AP) axis. This intercalation process involves planar cell polarity, anisotropic contractile forces along cell edges, and concerted cell deformation and movement. Although prior experiments have probed each of these factors separately, the connection among them remains unclear. This paper presents a chemo-mechanical model that integrates the three factors into a coherent framework. The model predicts the polarization of Rho-kinase, myosin and Bazooka downstream of an anisotropic Shroom distribution. In particular, myosin accumulates on cell edges along the DV axis, causing them to contract into a vertex. Subsequently, medial myosin in the cells anterior and posterior to the vertex helps to elongate it into a new edge parallel to the body axis. Thus, the tissue extends along the AP axis and narrows in the transverse direction through neighbor exchange. Model predictions of the polarity of the proteins and cell and tissue deformation are in good agreement with experimental observations.

  11. High efficiency solar cell processing

    NASA Technical Reports Server (NTRS)

    Ho, F.; Iles, P. A.

    1985-01-01

    At the time of writing, cells made by several groups are approaching 19% efficiency. General aspects of the processing required for such cells are discussed. Most processing used for high efficiency cells is derived from space-cell or concentrator cell technology, and recent advances have been obtained from improved techniques rather than from better understanding of the limiting mechanisms. Theory and modeling are fairly well developed, and adequate to guide further asymptotic increases in performance of near conventional cells. There are several competitive cell designs with promise of higher performance ( 20%) but for these designs further improvements are required. The available cell processing technology to fabricate high efficiency cells is examined.

  12. Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium.

    PubMed

    El-Hashash, Ahmed H K; Turcatel, Gianluca; Al Alam, Denise; Buckley, Sue; Tokumitsu, Hiroshi; Bellusci, Saverio; Warburton, David

    2011-04-01

    Cell polarity, mitotic spindle orientation and asymmetric division play a crucial role in the self-renewal/differentiation of epithelial cells, yet little is known about these processes and the molecular programs that control them in embryonic lung distal epithelium. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized with characteristic perpendicular cell divisions. Consistent with these findings, spindle orientation-regulatory proteins Insc, LGN (Gpsm2) and NuMA, and the cell fate determinant Numb are asymmetrically localized in embryonic lung distal epithelium. Interfering with the function of these proteins in vitro randomizes spindle orientation and changes cell fate. We further show that Eya1 protein regulates cell polarity, spindle orientation and the localization of Numb, which inhibits Notch signaling. Hence, Eya1 promotes both perpendicular division as well as Numb asymmetric segregation to one daughter in mitotic distal lung epithelium, probably by controlling aPKCζ phosphorylation. Thus, epithelial cell polarity and mitotic spindle orientation are defective after interfering with Eya1 function in vivo or in vitro. In addition, in Eya1(-/-) lungs, perpendicular division is not maintained and Numb is segregated to both daughter cells in mitotic epithelial cells, leading to inactivation of Notch signaling. As Notch signaling promotes progenitor cell identity at the expense of differentiated cell phenotypes, we test whether genetic activation of Notch could rescue the Eya1(-/-) lung phenotype, which is characterized by loss of epithelial progenitors, increased epithelial differentiation but reduced branching. Indeed, genetic activation of Notch partially rescues Eya1(-/-) lung epithelial defects. These findings uncover novel functions for Eya1 as a crucial regulator of the complex behavior of distal embryonic lung epithelium.

  13. Non-Uniform Membrane Diffusion Enables Steady-State Cell Polarization via Vesicular Trafficking

    PubMed Central

    Das, Arupratan; Smith, Sarah E.; Rubinstein, Boris; Li, Rong

    2013-01-01

    Actin-based vesicular trafficking of Cdc42, leading to a polarized concentration of the GTPase, has been implicated in cell polarization, but it was recently debated whether this mechanism allows stable maintenance of cell polarity. Here we show that endocytosis and exocytosis are spatially segregated in the polar plasma membrane, with sites of exocytosis correlating with microdomains of higher concentration and slower diffusion of Cdc42 compared to surrounding regions. Numerical simulations using experimentally obtained diffusion coefficients and trafficking geometry revealed that non-uniform membrane diffusion of Cdc42 in fact enables temporally sustained cell polarity. We show further that phosphatidylserine (PS), a phospholipid recently found to be crucial for cell polarity, is enriched in Cdc42 microdomains and weakening a potential interaction between PS and Cdc42 enhanced Cdc42 diffusion in the microdomains but impeded the strength of polarization. These findings demonstrate a critical role for membrane microdomains in vesicular trafficking mediated cell polarity. PMID:23340420

  14. Polarized fibronectin secretion induced by adenosine regulates bacterial–epithelial interaction in human intestinal epithelial cells

    PubMed Central

    2004-01-01

    Fibronectin (FN) is a multifunctional protein that plays important roles in many biological processes including cell adhesion and migration, wound healing and inflammation. Cellular FNs are produced by a wide variety of cell types including epithelial cells, which secrete them and often organize them into extensive extracellular matrices at their basal surface. However, regulation of FN synthesis and the polarity of FN secretion by intestinal epithelial cells have not been investigated. In the present study we investigated the role of adenosine, whose levels are up-regulated during inflammation, in modulating FN synthesis, the polarity of FN secretion and the downstream effects of the secreted FN. Polarized monolayers of T84 cells were used as an intestinal epithelial model. Adenosine added to either the apical or basolateral aspect of the cells led to a time- and dose-dependent accumulation of FN in the culture supernatants, polarized to the apical compartment and reached maximal levels 24 h after apical or basolateral addition of adenosine. Confocal microscopy confirmed that FN localized to the apical domain of model intestinal epithelial cells stimulated with apical or basolateral adenosine. The induction of FN was significantly down-regulated in response to the adenosine receptor antagonist alloxazine and was inhibited by cycloheximide. Moreover, adenosine increased FN promoter activity (3.5-fold compared with unstimulated controls) indicating that FN induction is, in part, transcriptionally regulated. Interestingly, we demonstrated that adenosine, as well as apical FN, significantly enhanced the adherence and invasion of Salmonella typhimurium into cultured epithelial cells. In summary, we have shown for the first time that FN, a classic extracellular matrix protein, is secreted into the apical compartment of epithelial cells in response to adenosine. FN may be a critical host factor that modulates adherence and invasion of bacteria, thus playing a key role

  15. Induction of Cell Polarization and Migration by a Gradient of Nanoscale Variations in Adhesive Ligand Spacing

    PubMed Central

    Arnold, Marco; Jakubick, Vera C.; Lohmüller, Theobald; Heil, Patrick; Blümmel, Jacques; Cavalcanti-Adam, Elisabetta A.; López-García, Mónica; Walther, Paul; Kessler, Horst; Geiger, Benjamin; Spatz, Joachim P.

    2013-01-01

    Cell interactions with adhesive surfaces play a vital role in the regulation of cell proliferation, viability and differentiation, and affect multiple biological processes. Since cell adhesion depends mainly on the nature and density of the adhesive ligand molecules, spatial molecular patterning, which enables the modulation of adhesion receptor clustering, might affect both the structural and signalling activities of the adhesive interaction. We herein show that cells plated on surfaces that present a molecularly defined spacing gradient of an integrin RGD ligand, can sense small but consistent differences in adhesive ligand spacing of about 1 nm across the cell diameter, which is approximately 61 μm when the spacing includes 70 nm. Consequently, these positional cues induce cell polarization, and initiate cell migration and signalling. We propose that differential positional clustering of the integrin transmembrane receptors is used by cells for exploring and interpreting their environment, at high spatial sensitivity. PMID:18558788

  16. Prickle/spiny-legs isoforms control the polarity of the apical microtubule network in planar cell polarity.

    PubMed

    Olofsson, Jessica; Sharp, Katherine A; Matis, Maja; Cho, Bomsoo; Axelrod, Jeffrey D

    2014-07-01

    Microtubules (MTs) are substrates upon which plus- and minus-end directed motors control the directional movement of cargos that are essential for generating cell polarity. Although centrosomal MTs are organized with plus-ends away from the MT organizing center, the regulation of non-centrosomal MT polarity is poorly understood. Increasing evidence supports the model that directional information for planar polarization is derived from the alignment of a parallel apical network of MTs and the directional MT-dependent trafficking of downstream signaling components. The Fat/Dachsous/Four-jointed (Ft/Ds/Fj) signaling system contributes to orienting those MTs. In addition to previously defined functions in promoting asymmetric subcellular localization of 'core' planar cell polarity (PCP) proteins, we find that alternative Prickle (Pk-Sple) protein isoforms control the polarity of this MT network. This function allows the isoforms of Pk-Sple to differentially determine the direction in which asymmetry is established and therefore, ultimately, the direction of tissue polarity. Oppositely oriented signals that are encoded by oppositely oriented Fj and Ds gradients produce the same polarity outcome in different tissues or compartments, and the tissue-specific activity of alternative Pk-Sple protein isoforms has been observed to rectify the interpretation of opposite upstream directional signals. The control of MT polarity, and thus the directionality of apical vesicle traffic, by Pk-Sple provides a mechanism for this rectification.

  17. Basics of Polar-Format algorithm for processing Synthetic Aperture Radar images.

    SciTech Connect

    Doerry, Armin Walter

    2012-05-01

    The purpose of this report is to provide a background to Synthetic Aperture Radar (SAR) image formation using the Polar Format (PFA) processing algorithm. This is meant to be an aid to those tasked to implement real-time image formation using the Polar Format processing algorithm.

  18. The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity

    PubMed Central

    Narayanan, Anjana S.; Reyes, Steve B.; Um, Kyongmi; McCarty, Joseph H.; Tolias, Kimberley F.

    2013-01-01

    Cell polarization is essential for many biological processes, including directed cell migration, and loss of polarity contributes to pathological conditions such as cancer. The Par complex (Par3, Par6, and PKCζ) controls cell polarity in part by recruiting the Rac-specific guanine nucleotide exchange factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal remodeling. However, the mechanisms that restrict Par-Tiam1 complex activity to the leading edge to maintain cell polarity during migration remain unclear. We identify the Rac-specific GTPase-activating protein (GAP) breakpoint cluster region protein (Bcr) as a novel regulator of the Par-Tiam1 complex. We show that Bcr interacts with members of the Par complex and inhibits both Rac1 and PKCζ signaling. Loss of Bcr results in faster, more random migration and striking polarity defects in astrocytes. These polarity defects are rescued by reducing PKCζ activity or by expressing full-length Bcr, but not an N-terminal deletion mutant or the homologous Rac-GAP, Abr, both of which fail to associate with the Par complex. These results demonstrate that Bcr is an integral member of the Par-Tiam1 complex that controls polarized cell migration by locally restricting both Rac1 and PKCζ function. PMID:24152735

  19. Endothelial cell polarization and chemotaxis in a microfluidic device.

    PubMed

    Shamloo, Amir; Ma, Ning; Poo, Mu-Ming; Sohn, Lydia L; Heilshorn, Sarah C

    2008-08-01

    The directed migration of endothelial cells is an early and critical step in angiogenesis, or new blood vessel formation. In this study, the polarization and chemotaxis of human umbilical vein endothelial cells (HUVEC) in response to quantified gradients of vascular endothelial growth factor (VEGF) were examined. To accomplish this, a microfluidic device was designed and fabricated to generate stable concentration gradients of biomolecules in a cell culture chamber while minimizing the fluid shear stress experienced by the cells. Finite element simulation of the device geometry produced excellent agreement with the observed VEGF concentration distribution, which was found to be stable across multiple hours. This device is expected to have wide applicability in the study of shear-sensitive cells such as HUVEC and non-adherent cell types as well as in the study of migration through three-dimensional matrices. HUVEC were observed to chemotax towards higher VEGF concentrations across the entire range of concentrations studied (18-32 ng mL(-1)) when the concentration gradient was 14 ng mL(-1) mm(-1). In contrast, shallow gradients (2 ng mL(-1) mm(-1)) across the same concentration range were unable to induce HUVEC chemotaxis. Furthermore, while all HUVEC exposed to elevated VEGF levels (both in steep and shallow gradients) displayed an increased number of filopodia, only chemotaxing HUVEC displayed an asymmetric distribution of filopodia, with enhanced numbers of protrusions present along the leading edge. These results suggest a two-part requirement to induce VEGF chemotaxis: the VEGF absolute concentration enhances the total number of filopodia extended while the VEGF gradient steepness induces filopodia localization, cell polarization, and subsequent directed migration.

  20. Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

    PubMed Central

    Sajjan, Umadevi; Wang, Qiong; Zhao, Ying; Gruenert, Dieter C.; Hershenson, Marc B.

    2008-01-01

    Rationale: Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease. Objectives: We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection. Methods: Primary human airway epithelial cells grown at air–liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (RT) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting. Measurements and Main Results: Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV- but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in RT without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease RT, suggesting a requirement for viral replication. Reduced RT was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-α, IFN-γ and IL-1β reversed corresponding cytokine-induced reductions in RT but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo. Conclusions: RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function. PMID:18787220

  1. Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization.

    PubMed

    Chen, Min-Min; Xiao, Xiao; Lao, Xiang-Ming; Wei, Yuan; Liu, Rui-Xian; Zeng, Qiu-Hui; Wang, Jun-Cheng; Ouyang, Fang-Zhu; Chen, Dong-Ping; Chan, Ka-Wo; Shi, Dai-Chao; Zheng, Limin; Kuang, Dong-Ming

    2016-10-01

    The existence, regulation, and functions of IL21(+) immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21(+) TFH-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4(+) T-cell population at levels comparable with the TFH cells present in lymph nodes. However, these TFH-like cells displayed a unique CXCR5(-)PD-1(lo/-)BTLA(-)CD69(hi) tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of TFH cells. Toll-like receptor 4 (TLR4)-elicited innate monocyte inflammation was important for IL21(+) TFH-like cell induction in tumors, and activation of STAT1 and STAT3 was critical for TFH-like cell polarization in this process. Importantly, the TFH-like cells operated in IL21-IFNγ-dependent pathways to induce plasma cell differentiation and thereby create conditions for protumorigenic M2b macrophage polarization and cancer progression. Thus, induction of TFH-like cells links innate inflammation to immune privilege in tumors. We identified a novel protumorigenic IL21(+) TFH-like cell subset with a CXCR5(-)PD-1(-) BTLA(-)CD69(hi) tissue-resident phenotype in hepatoma. TLR4-mediated monocyte inflammation and subsequent T-cell STAT1 and STAT3 activation are critical for TFH-like cell induction. TFH-like cells operate via IL21-IFNγ pathways to induce plasma cells and create conditions for M2b macrophage polarization. Cancer Discov; 6(10); 1182-95. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069. 2016 American Association for Cancer Research.

  2. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia

    PubMed Central

    Rolls, Melissa M.; Albertson, Roger; Shih, Hsin-Pei; Lee, Cheng-Yu; Doe, Chris Q.

    2003-01-01

    Cell polarity is essential for generating cell diversity and for the proper function of most differentiated cell types. In many organisms, cell polarity is regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6 proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid-larval stages, where they exhibit defects in neuroblast and epithelial cell polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation. Mutant imaginal disc epithelia have defects in apical/basal cell polarity and tissue morphology. In addition, we show that aPKC mutants show reduced cell proliferation in both neuroblasts and epithelia, the opposite of the lethal giant larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly suppress most lgl cell polarity and overproliferation phenotypes. PMID:14657233

  3. POC in the process of acquiring polarization characteristics

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaojun; Cao, Ercong; Gu, Guohua; Qian, Weixian; Yang, Wei; Zhang, Haiyue

    2016-09-01

    Considering the change of optical information on material surface, this paper proposes a useful notion called pixel-level optical constants (POC). Through Fresnel equations, traditional optical constants (refractive index n and extinction coefficient k ) can reflect photoelectric characteristics on material surface. Combining with Mueller calculus in polarization optics, POC can describe the distrbution of photoelectric characteristics on material surface. POC is mainly calculated by the decomposition of Mueller matrix which includes Fresnel amplitude, ratio of two orthogonal reflection coefficient component P and variation of phase difference between incident light and reflected light Δ . With the regularity of polarized light and the statistics of Mueller matrices, optical characteristics can be detailed to each pixel in POC, which will independently show the distribution of polarization characteristics on material surface. And it can also be approximately averaged to obtain traditional optical constants. So POC is significant to optical researches on material surface.

  4. The planar cell polarity pathway directs parietal endoderm migration.

    PubMed

    LaMonica, Kristi; Bass, Maya; Grabel, Laura

    2009-06-01

    Parietal endoderm (PE) contributes to the yolk sac and is the first migratory cell type in the mammalian embryo. We can visualize PE migration in vitro using the F9 teratocarcinoma derived embryoid body outgrowth system and, show here that PE migration is directed by the non-canonical Wnt planar cell polarity (PCP) pathway via Rho/ROCK. Based on golgi apparatus localization and microtubule orientation, 68.6% of cells in control outgrowths are oriented in the direction of migration. Perturbation of Wnt signaling via sFRP treatment results in a loss of orientation coupled with an increase in cell migration. Inhibition of the PCP pathway at the level of Daam1 also results in a loss of cell orientation along with an increase in cell migration, as seen with sFRP treatment. Constitutively active Daam can inhibit the loss of orientation that occurs with sFRP treatment. We previously demonstrated that ROCK inhibition leads to an increase in cell migration, and we now show that these cells also lack oriented migration. Canonical Wnt signaling or the Rac arm of the PCP pathway does not appear to play a role in PE oriented migration. These data suggest the PCP pathway via Rho/ROCK modulates migration of PE.

  5. Topographic cell instructive patterns to control cell adhesion, polarization and migration

    PubMed Central

    Ventre, Maurizio; Natale, Carlo Fortunato; Rianna, Carmela; Netti, Paolo Antonio

    2014-01-01

    Topographic patterns are known to affect cellular processes such as adhesion, migration and differentiation. However, the optimal way to deliver topographic signals to provide cells with precise instructions has not been defined yet. In this work, we hypothesize that topographic patterns may be able to control the sensing and adhesion machinery of cells when their interval features are tuned on the characteristic lengths of filopodial probing and focal adhesions (FAs). Features separated by distance beyond the length of filopodia cannot be readily perceived; therefore, the formation of new adhesions is discouraged. If, however, topographic features are separated by a distance within the reach of filopodia extension, cells can establish contact between adjacent topographic islands. In the latter case, cell adhesion and polarization rely upon the growth of FAs occurring on a specific length scale that depends on the chemical properties of the surface. Topographic patterns and chemical properties may interfere with the growth of FAs, thus making adhesions unstable. To test this hypothesis, we fabricated different micropatterned surfaces displaying feature dimensions and adhesive properties able to interfere with the filopodial sensing and the adhesion maturation, selectively. Our data demonstrate that it is possible to exert a potent control on cell adhesion, elongation and migration by tuning topographic features’ dimensions and surface chemistry. PMID:25253035

  6. Planar cell polarity links axes of spatial dynamics in neural-tube closure.

    PubMed

    Nishimura, Tamako; Honda, Hisao; Takeichi, Masatoshi

    2012-05-25

    Neural-tube closure is a critical step of embryogenesis, and its failure causes serious birth defects. Coordination of two morphogenetic processes--convergent extension and neural-plate apical constriction--ensures the complete closure of the neural tube. We now provide evidence that planar cell polarity (PCP) signaling directly links these two processes. In the bending neural plates, we find that a PCP-regulating cadherin, Celsr1, is concentrated in adherens junctions (AJs) oriented toward the mediolateral axes of the plates. At these AJs, Celsr1 cooperates with Dishevelled, DAAM1, and the PDZ-RhoGEF to upregulate Rho kinase, causing their actomyosin-dependent contraction in a planar-polarized manner. This planar-polarized contraction promotes simultaneous apical constriction and midline convergence of neuroepithelial cells. Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Polarizing intestinal epithelial cells electrically through Ror2

    PubMed Central

    Cao, Lin; McCaig, Colin D.; Scott, Roderick H.; Zhao, Siwei; Milne, Gillian; Clevers, Hans; Zhao, Min; Pu, Jin

    2014-01-01

    ABSTRACT The apicobasal polarity of enterocytes determines where the brush border membrane (apical membrane) will form, but how this apical membrane faces the lumen is not well understood. The electrical signal across the epithelium could serve as a coordinating cue, orienting and polarizing enterocytes. Here, we show that applying a physiological electric field to intestinal epithelial cells, to mimic the natural electric field created by the transepithelial potential difference, polarized phosphorylation of the actin-binding protein ezrin, increased expression of intestinal alkaline phosphatase (ALPI, a differentiation marker) and remodeled the actin cytoskeleton selectively on the cathode side. In addition, an applied electric field also activated ERK1/2 and LKB1 (also known as STK11), key molecules in apical membrane formation. Disruption of the tyrosine protein kinase transmembrane receptor Ror2 suppressed activation of ERK1/2 and LKB1 significantly, and subsequently inhibited apical membrane formation in enterocytes. Our findings indicate that the endogenous electric field created by the transepithelial potential difference might act as an essential coordinating signal for apical membrane formation at a tissue level, through activation of LKB1 mediated by Ror2–ERK signaling. PMID:24928904

  8. A mechanism for cell motility by active polar gels

    PubMed Central

    Marth, W.; Praetorius, S.; Voigt, A.

    2015-01-01

    We analyse a generic motility model, with the motility mechanism arising by contractile stress due to the interaction of myosin and actin. A hydrodynamic active polar gel theory is used to model the cytoplasm of a cell and is combined with a Helfrich-type model to account for membrane properties. The overall model allows consideration of the motility without the necessity for local adhesion. Besides a detailed numerical approach together with convergence studies for the highly nonlinear free boundary problem, we also compare the induced flow field of the motile cell with that of classical squirmer models and identify the motile cell as a puller or pusher, depending on the strength of the myosin–actin interactions. PMID:25926698

  9. Stomatal development: a plant's perspective on cell polarity, cell fate transitions and intercellular communication

    PubMed Central

    Lau, On Sun; Bergmann, Dominique C.

    2012-01-01

    The plant stomatal lineage manifests features common to many developmental contexts: precursor cells are chosen from an initially equivalent field of cells, undergo asymmetric and self-renewing divisions, communicate among themselves and respond to information from a distance. As we review here, the experimental accessibility of these epidermal lineages, particularly in Arabidopsis, has made stomata a conceptual and technical framework for the study of cell fate, stem cells, and cell polarity in plants. PMID:22991435

  10. Stomatal development: a plant's perspective on cell polarity, cell fate transitions and intercellular communication.

    PubMed

    Lau, On Sun; Bergmann, Dominique C

    2012-10-01

    The plant stomatal lineage manifests features common to many developmental contexts: precursor cells are chosen from an initially equivalent field of cells, undergo asymmetric and self-renewing divisions, communicate among themselves and respond to information from a distance. As we review here, the experimental accessibility of these epidermal lineages, particularly in Arabidopsis, has made stomata a conceptual and technical framework for the study of cell fate, stem cells, and cell polarity in plants.

  11. Coordination of planar cell polarity pathways through Spiny-legs

    PubMed Central

    Ambegaonkar, Abhijit A; Irvine, Kenneth D

    2015-01-01

    Morphogenesis and physiology of tissues and organs requires planar cell polarity (PCP) systems that orient and coordinate cells and their behaviors, but the relationship between PCP systems has been controversial. We have characterized how the Frizzled and Dachsous-Fat PCP systems are connected through the Spiny-legs isoform of the Prickle-Spiny-legs locus. Two different components of the Dachsous-Fat system, Dachsous and Dachs, can each independently interact with Spiny-legs and direct its localization in vivo. Through characterization of the contributions of Prickle, Spiny-legs, Dachsous, Fat, and Dachs to PCP in the Drosophila wing, eye, and abdomen, we define where Dachs-Spiny-legs and Dachsous-Spiny-legs interactions contribute to PCP, and provide a new understanding of the orientation of polarity and the basis of PCP phenotypes. Our results support the direct linkage of PCP systems through Sple in specific locales, while emphasizing that cells can be subject to and must ultimately resolve distinct, competing PCP signals. DOI: http://dx.doi.org/10.7554/eLife.09946.001 PMID:26505959

  12. Morphological and functional characterization of bovine oviductal epithelial cell monolayers cultured on polarizing membranes.

    PubMed

    Gómez, E; Uría, H

    1997-01-01

    Several characteristics of oviductal cells, cultured under either polarizing or nonpolarizing conditions, were studied. In vitro produced bovine embryos tested the embryotrophic abilities of the respective conditioned media. Conditioned medium from the apical face of polarized cell monolayers supported higher rates of development to blastocyst and expanded blastocysts. In contrast, conditioned medium from the basal face supported embryo development only to the 8-16 cell stage; however, these embryos were able to continue development to the morula stage when cultured in medium from the apical and basal faces, indicating total cell confluence and a clear functional polarization. At the ultrastructural level, cells cultured in polarizing conditions displayed characteristics nearer to the same cells in vivo and signs of a metabolic activity higher than that in cells cultured under non-polarizing conditions. It can be concluded that cell-polarization, in our culture conditions, is beneficial to embryo development.

  13. Geometry-Driven Polarity in Motile Amoeboid Cells.

    PubMed

    Nagel, Oliver; Guven, Can; Theves, Matthias; Driscoll, Meghan; Losert, Wolfgang; Beta, Carsten

    2014-01-01

    Motile eukaryotic cells, such as leukocytes, cancer cells, and amoeba, typically move inside the narrow interstitial spacings of tissue or soil. While most of our knowledge of actin-driven eukaryotic motility was obtained from cells that move on planar open surfaces, recent work has demonstrated that confinement can lead to strongly altered motile behavior. Here, we report experimental evidence that motile amoeboid cells undergo a spontaneous symmetry breaking in confined interstitial spaces. Inside narrow channels, the cells switch to a highly persistent, unidirectional mode of motion, moving at a constant speed along the channel. They remain in contact with the two opposing channel side walls and alternate protrusions of their leading edge near each wall. Their actin cytoskeleton exhibits a characteristic arrangement that is dominated by dense, stationary actin foci at the side walls, in conjunction with less dense dynamic regions at the leading edge. Our experimental findings can be explained based on an excitable network model that accounts for the confinement-induced symmetry breaking and correctly recovers the spatio-temporal pattern of protrusions at the leading edge. Since motile cells typically live in the narrow interstitial spacings of tissue or soil, we expect that the geometry-driven polarity we report here plays an important role for movement of cells in their natural environment.

  14. Interhemispheric Differences in Dentifrication and Related Processes Affecting Polar Ozone

    NASA Technical Reports Server (NTRS)

    Santee, M. L.; Read, W. G.; Waters, J. W.; Froidevaux, L.; Manney, G. L.; Flower, D. A.; Jarnot, R. F.; Harwood, R. S.; Peckham, G. E.

    1994-01-01

    The severe depletion of stratospheric ozone over Antarctica in late winter and early spring is caused by enhanced CLO abundances arising from heterogeneous reactions on polar stratospheric clouds (PSCs). CLO abundances comparable to those over Antarctica have also been observed throughout the Arctic Vortex, but the accompanying loss of Arctic ozone has been much less severe.

  15. Studies of interactive plasma processes in the polar cusp

    NASA Technical Reports Server (NTRS)

    Waite, J. Hunter, Jr.

    1992-01-01

    The final report for NAGW-1657 (SwRI Project 15-2783) is presented. Several distinctly different areas of research are discussed: (1) studies of the thermal structure of polar outflows; (2) Prognoz-8 data analysis; and (3) the Ulysses Jupiter encounter.

  16. Interhemispheric Differences in Dentifrication and Related Processes Affecting Polar Ozone

    NASA Technical Reports Server (NTRS)

    Santee, M. L.; Read, W. G.; Waters, J. W.; Froidevaux, L.; Manney, G. L.; Flower, D. A.; Jarnot, R. F.; Harwood, R. S.; Peckham, G. E.

    1994-01-01

    The severe depletion of stratospheric ozone over Antarctica in late winter and early spring is caused by enhanced CLO abundances arising from heterogeneous reactions on polar stratospheric clouds (PSCs). CLO abundances comparable to those over Antarctica have also been observed throughout the Arctic Vortex, but the accompanying loss of Arctic ozone has been much less severe.

  17. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells

    PubMed Central

    Drummond, Coyne G.

    2015-01-01

    ABSTRACT Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and

  18. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    PubMed

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  19. Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma

    PubMed Central

    Dumars, Clotilde; Ngyuen, Jean-Michel; Gaultier, Aurélie; Lanel, Rachel; Corradini, Nadège; Gouin, François; Heymann, Dominique; Heymann, Marie-Françoise

    2016-01-01

    Osteosarcoma (OS) is the most common bone sarcoma in adolescents, and has poor prognosis. A vicious cycle is established between OS cells and their microenvironment in order to facilitate the tumor growth and cell spreading. The present work aims to better characterize the tumor microenvironment in OS in order to identify new therapeutic targets relating to metastatic process. Tissue microarrays of pre-chemotherapy OS biopsies were used for characterizing the tumor niche by immunohistochemistry. Parameters studies included: immune cells (M1, M2-subtypes of tumor-associated macrophages (TAM); T, B lymphocytes; mast cells), vascularization (endothelial, perivascular cells), OPG, RANKL, and mitotic index. Two groups of patients were defined, 22 localized OS (OS Meta-) and 28 metastatic OS (OS Meta+). The OS Meta- group was characterized by a higher infiltration of INOS+ M1-polarizedmacrophages and upregulated OPG immunostaining. OS Meta+ tumors showed a significant increase in CD146+ cells. INOS+ M1-macrophages were correlated with OPG staining, and negatively with the presence of metastases. CD163+ M2-macrophages were positively correlated with CD146+ cells. In multivariate analysis, INOS and OPG were predictive factors for metastasis. An older age, non-metastatic tumor, good response to chemotherapy, and higher macrophage infiltration were significantly associated with better overall survival. TAMs are associated with better overall survival and a dysregulation of M1/M2 polarized-macrophages in favor of M1 subtype was observed in non-metastatic OS. PMID:27823976

  20. Ectopic KNOX Expression Affects Plant Development by Altering Tissue Cell Polarity and Identity.

    PubMed

    Richardson, Annis Elizabeth; Rebocho, Alexandra B; Coen, Enrico S

    2016-08-23

    Plant development involves two polarity types: tissue cell (asymmetries within cells are coordinated across tissues) and regional (identities vary spatially across tissues) polarity. Both appear altered in the barley (Hordeum vulgare) Hooded mutant, in which ectopic expression of the KNOTTED1-like Homeobox (KNOX) gene, BKn3, causes inverted polarity of differentiated hairs and ectopic flowers, in addition to wing-shaped outgrowths. These lemma-specific effects allow the spatiotemporal analysis of events following ectopic BKn3 expression, determining the relationship between KNOXs, polarity, and shape. We show that tissue cell polarity, based on localization of the auxin transporter SISTER OF PINFORMED1 (SoPIN1), dynamically reorients as ectopic BKn3 expression increases. Concurrently, ectopic expression of the auxin importer LIKE AUX1 and boundary gene NO APICAL MERISTEM is activated. The polarity of hairs reflects SoPIN1 patterns, suggesting that tissue cell polarity underpins oriented cell differentiation. Wing cell files reveal an anisotropic growth pattern, and computational modeling shows how polarity guiding growth can account for this pattern and wing emergence. The inverted ectopic flower orientation does not correlate with SoPIN1, suggesting that this form of regional polarity is not controlled by tissue cell polarity. Overall, the results suggest that KNOXs trigger different morphogenetic effects through interplay between tissue cell polarity, identity, and growth.

  1. Ectopic KNOX Expression Affects Plant Development by Altering Tissue Cell Polarity and Identity[OPEN

    PubMed Central

    Rebocho, Alexandra B.

    2016-01-01

    Plant development involves two polarity types: tissue cell (asymmetries within cells are coordinated across tissues) and regional (identities vary spatially across tissues) polarity. Both appear altered in the barley (Hordeum vulgare) Hooded mutant, in which ectopic expression of the KNOTTED1-like Homeobox (KNOX) gene, BKn3, causes inverted polarity of differentiated hairs and ectopic flowers, in addition to wing-shaped outgrowths. These lemma-specific effects allow the spatiotemporal analysis of events following ectopic BKn3 expression, determining the relationship between KNOXs, polarity, and shape. We show that tissue cell polarity, based on localization of the auxin transporter SISTER OF PINFORMED1 (SoPIN1), dynamically reorients as ectopic BKn3 expression increases. Concurrently, ectopic expression of the auxin importer LIKE AUX1 and boundary gene NO APICAL MERISTEM is activated. The polarity of hairs reflects SoPIN1 patterns, suggesting that tissue cell polarity underpins oriented cell differentiation. Wing cell files reveal an anisotropic growth pattern, and computational modeling shows how polarity guiding growth can account for this pattern and wing emergence. The inverted ectopic flower orientation does not correlate with SoPIN1, suggesting that this form of regional polarity is not controlled by tissue cell polarity. Overall, the results suggest that KNOXs trigger different morphogenetic effects through interplay between tissue cell polarity, identity, and growth. PMID:27553356

  2. The Spindle Orientation Machinery Beyond Mitosis: When Cell Specialization Demands Polarization.

    PubMed

    Tadenev, Abigail L D; Tarchini, Basile

    2017-01-01

    Mitosis is a process requiring strict spatial organization of cellular components. In particular, the orientation of the mitotic spindle with respect to the tissue defines the division plane. In turn, the orientation of cell division can regulate tissue morphology or the fate of daughter cells. While we have learned much about the mechanisms of mitotic spindle orientation, recent studies suggest that the proteins implicated can also play important roles in post-mitotic cells. Interestingly, post-mitotic protein function often involves polarizing the cell cytoskeleton during differentiation, mirroring its ability to orient the mitotic spindle during division. This review focuses on alternative functions of the spindle orientation machinery after division, when the cell undergoes a specialization process associated with differentiation or mature function, and discusses diseases associated to those alternative functions.

  3. Trafficking through COPII Stabilises Cell Polarity and Drives Secretion during Drosophila Epidermal Differentiation

    PubMed Central

    Norum, Michaela; Tång, Erika; Chavoshi, Tina; Schwarz, Heinz; Linke, Dirk; Uv, Anne; Moussian, Bernard

    2010-01-01

    Background The differentiation of an extracellular matrix (ECM) at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation. Principal Findings We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus. Conclusion Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes. PMID:20520821

  4. Dchs1–Fat4 regulation of polarized cell behaviours during skeletal morphogenesis

    PubMed Central

    Mao, Yaopan; Kuta, Anna; Crespo-Enriquez, Ivan; Whiting, Danielle; Martin, Tina; Mulvaney, Joanna; Irvine, Kenneth D.; Francis-West, Philippa

    2016-01-01

    Skeletal shape varies widely across species as adaptation to specialized modes of feeding and locomotion, but how skeletal shape is established is unknown. An example of extreme diversity in the shape of a skeletal structure can be seen in the sternum, which varies considerably across species. Here we show that the Dchs1–Fat4 planar cell polarity pathway controls cell orientation in the early skeletal condensation to define the shape and relative dimensions of the mouse sternum. These changes fit a model of cell intercalation along differential Dchs1–Fat4 activity that drives a simultaneous narrowing, thickening and elongation of the sternum. Our results identify the regulation of cellular polarity within the early pre-chondrogenic mesenchyme, when skeletal shape is established, and provide the first demonstration that Fat4 and Dchs1 establish polarized cell behaviour intrinsically within the mesenchyme. Our data also reveal the first indication that cell intercalation processes occur during ventral body wall elongation and closure. PMID:27145737

  5. Polar/apolar chemical inducers of differentiation of transformed cells: strategies to improve therapeutic potential.

    PubMed Central

    Marks, P A; Breslow, R; Rifkind, R A; Ngo, L; Singh, R

    1989-01-01

    N,N'-Hexamethylenebisacetamide (HMBA) induces transformed cells to differentiate, accompanied by suppression of oncogenicity. Clinical trials have shown that HMBA can cause positive therapeutic responses in some cancer patients, but clinical efficacy may be limited, in part, by dose-related toxicity. Potential improvements in efficacy may be accomplished by changes in the chemical structure of inducing agents and by increasing the sensitivity of tumor cells to inducers of differentiation. We have previously described an approach to improving tumor cell responsiveness to inducing agents. Transformed cell lines that have acquired low levels of resistance to vincristine display a markedly increased sensitivity to HMBA. We now report on a series of hybrid polar/apolar compounds--some of which are as active as HMBA and several of which are significantly more active than HMBA in vitro--whose chemical structures make it likely that they have different pharmacokinetics. Vincristine-resistant murine erythroleukemia cells also are shown to have marked increased sensitivity to these hybrid polar/apolar compounds. Thus these findings suggest potentially useful strategies for the application of polar/apolar inducers of differentiation to the treatment of cancers. These studies also provide approaches to further understanding of the biological process of terminal differentiation. PMID:2762329

  6. Epstein-Barr Virus Transcytosis through Polarized Oral Epithelial Cells

    PubMed Central

    Herrera, Rossana; Palefsky, Joel M.

    2013-01-01

    Although Epstein-Barr virus (EBV) is an orally transmitted virus, viral transmission through the oropharyngeal mucosal epithelium is not well understood. In this study, we investigated how EBV traverses polarized human oral epithelial cells without causing productive infection. We found that EBV may be transcytosed through oral epithelial cells bidirectionally, from both the apical to the basolateral membranes and the basolateral to the apical membranes. Apical to basolateral EBV transcytosis was substantially reduced by amiloride, an inhibitor of macropinocytosis. Electron microscopy showed that virions were surrounded by apical surface protrusions and that virus was present in subapical vesicles. Inactivation of signaling molecules critical for macropinocytosis, including phosphatidylinositol 3-kinases, myosin light-chain kinase, Ras-related C3 botulinum toxin substrate 1, p21-activated kinase 1, ADP-ribosylation factor 6, and cell division control protein 42 homolog, led to significant reduction in EBV apical to basolateral transcytosis. In contrast, basolateral to apical EBV transcytosis was substantially reduced by nystatin, an inhibitor of caveolin-mediated virus entry. Caveolae were detected in the basolateral membranes of polarized human oral epithelial cells, and virions were detected in caveosome-like endosomes. Methyl β-cyclodextrin, an inhibitor of caveola formation, reduced EBV basolateral entry. EBV virions transcytosed in either direction were able to infect B lymphocytes. Together, these data show that EBV transmigrates across oral epithelial cells by (i) apical to basolateral transcytosis, potentially contributing to initial EBV penetration that leads to systemic infection, and (ii) basolateral to apical transcytosis, which may enable EBV secretion into saliva in EBV-infected individuals. PMID:23698302

  7. Differential sensitivity of epithelial cells to extracellular matrix in polarity establishment.

    PubMed

    Yonemura, Shigenobu

    2014-01-01

    Establishment of apical-basal polarity is crucial for epithelial sheets that form a compartment in the body, which function to maintain the environment in the compartment. Effects of impaired polarization are easily observed in three-dimensional (3-D) culture systems rather than in two-dimensional (2-D) culture systems. Although the mechanisms for establishing the polarity are not completely understood, signals from the extracellular matrix (ECM) are considered to be essential for determining the basal side and eventually generating polarity in the epithelial cells. To elucidate the common features and differences in polarity establishment among various epithelial cells, we analyzed the formation of epithelial apical-basal polarity using three cell lines of different origin: MDCK II cells (dog renal tubules), EpH4 cells (mouse mammary gland), and R2/7 cells (human colon) expressing wild-type α-catenin (R2/7 α-Cate cells). These cells showed clear apical-basal polarity in 2-D cultures. In 3-D cultures, however, each cell line displayed different responses to the same ECM. In MDCK II cells, spheroids with a single lumen formed in both Matrigel and collagen gel. In R2/7 α-Cate cells, spheroids showed similar apical-basal polarity as that seen in MDCK II cells, but had multiple lumens. In EpH4 cells, the spheroids displayed an apical-basal polarity that was opposite to that seen in the other two cell types in both ECM gels, at least during the culture period. On the other hand, the three cell lines showed the same apical-basal polarity both in 2-D cultures and in 3-D cultures using the hanging drop method. The three lines also had similar cellular responses to ECM secreted by the cells themselves. Therefore, appropriate culture conditions should be carefully determined in advance when using various epithelial cells to analyze cell polarity or 3-D morphogenesis.

  8. Planar cell polarity in the mammalian eye lens

    PubMed Central

    Sugiyama, Yuki; Lovicu, Frank J

    2011-01-01

    The major role of the eye lens is to transmit and focus images onto the retina. For this function, the lens needs to develop and maintain the correct shape, notably, the precise curvature and high-level order and organization of its elements. The lens is mainly comprised of highly elongated fiber cells with hexagonal cross-sectional profiles that facilitate regular packing. Collectively, they form concentrically arranged layers around the anterior-posterior polar axis, and their convex curvature contributes to the spheroidal shape of the lens. Although the lens has been a popular system for developmental studies, little is known about the mechanism(s) that underlies the development of its exquisite three-dimensional cellular architecture. In this review, we will describe our recent work, which shows how planar cell polarity (PCP) operates in lens and contributes to its morphogenesis. We believe that the lens will be a useful model system to study PCP in general and gain insights into mechanisms that generate high-level cellular order during development. PMID:22027540

  9. Planar cell polarity in the mammalian eye lens.

    PubMed

    Sugiyama, Yuki; Lovicu, Frank J; McAvoy, John W

    2011-01-01

    The major role of the eye lens is to transmit and focus images onto the retina. For this function, the lens needs to develop and maintain the correct shape, notably, the precise curvature and high-level order and organization of its elements. The lens is mainly comprised of highly elongated fiber cells with hexagonal cross-sectional profiles that facilitate regular packing. Collectively, they form concentrically arranged layers around the anterior-posterior polar axis, and their convex curvature contributes to the spheroidal shape of the lens. Although the lens has been a popular system for developmental studies, little is known about the mechanism(s) that underlies the development of its exquisite three-dimensional cellular architecture. In this review, we will describe our recent work, which shows how planar cell polarity (PCP) operates in lens and contributes to its morphogenesis. We believe that the lens will be a useful model system to study PCP in general and gain insights into mechanisms that generate high-level cellular order during development.

  10. The cell polarity determinant CDC42 controls division symmetry to block leukemia cell differentiation.

    PubMed

    Mizukawa, Benjamin; O'Brien, Eric; Moreira, Daniel C; Wunderlich, Mark; Hochstetler, Cindy L; Duan, Xin; Liu, Wei; Orr, Emily; Grimes, H Leighton; Mulloy, James C; Zheng, Yi

    2017-09-14

    As a central regulator of cell polarity, the activity of CDC42 GTPase is tightly controlled in maintaining normal hematopoietic stem and progenitor cell (HSC/P) functions. We found that transformation of HSC/P to acute myeloid leukemia (AML) is associated with increased CDC42 expression and activity in leukemia cells. In a mouse model of AML, the loss of Cdc42 abrogates MLL-AF9-induced AML development. Furthermore, genetic ablation of CDC42 in both murine and human MLL-AF9 (MA9) cells decreased survival and induced differentiation of the clonogenic leukemia-initiating cells. We show that MLL-AF9 leukemia cells maintain cell polarity in the context of elevated Cdc42-guanosine triphosphate activity, similar to nonmalignant, young HSC/Ps. The loss of Cdc42 resulted in a shift to depolarized AML cells that is associated with a decrease in the frequency of symmetric and asymmetric cell divisions producing daughter cells capable of self-renewal. Importantly, we demonstrate that inducible CDC42 suppression in primary human AML cells blocks leukemia progression in a xenograft model. Thus, CDC42 loss suppresses AML cell polarity and division asymmetry, and CDC42 constitutes a useful target to alter leukemia-initiating cell fate for differentiation therapy. © 2017 by The American Society of Hematology.

  11. Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo.

    PubMed

    Meyen, Dana; Tarbashevich, Katsiaryna; Banisch, Torsten U; Wittwer, Carolina; Reichman-Fried, Michal; Maugis, Benoît; Grimaldi, Cecilia; Messerschmidt, Esther-Maria; Raz, Erez

    2015-04-15

    Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue.

  12. Involvement of LIM kinase 1 in actin polarization in human CD4 T cells

    PubMed Central

    Xu, Xuehua; Guo, Jia; Vorster, Paul; Wu, Yuntao

    2012-01-01

    Chemokine binding to cognate receptors induces actin dynamics that are a major driving force for T cell migration and chemotactic motility. HIV-1 binding to the chemokine coreceptor CXCR4 initiates chemotactic signaling, mimicking chemokine-induced actin dynamics to facilitate infection processes such as entry, early DNA synthesis, and nuclear migration. Recently, we identified that HIV-triggered early actin polymerization is mediated through the Rac1-PAK1/2-LIMK1-cofilin pathway. Inhibition of LIMK1 (LIM domain kinase 1), a kinase phosphorylating cofilin, through shRNA knockdown decreases actin polymerization and T cell chemotaxis toward SDF-1. The LIMK1 knockdown T cells also supported lower viral entry, DNA synthesis and nuclear migration, suggesting a critical role of LIMK1-mediated actin dynamics in the initiation of HIV-1 infection. Surprisingly, LIMK1 knockdown in CEM-SS T cells did not lead to an overall change in the ratio of phospho-cofilin to total cofilin although there was a measurable decrease in the amount of actin filaments in cells. The decrease in filamentous actin in LIMK1 knockdown cells was found to mainly occur in polarized cap region rich in F-actin. These results suggest that LIMK1 may be involved in spontaneous actin polarization in transformed T cells. The inhibition of T cell chemotaxis by LIMK1 knockdown likely result from inhibition of localized LIMK1 activation and cofilin phosphorylation that are required for polarized actin polymerization for directional cell migration. The inhibition of HIV-1 infection by LIMK1 knockdown may also result from the decrease of actin-rich membrane protrusions that may be preferred viral entry sites in T cells. PMID:23060964

  13. Cell Fate Determination and the Switch from Diffuse Growth to Planar Polarity in Arabidopsis Root Epidermal Cells

    PubMed Central

    Balcerowicz, Daria; Schoenaers, Sébastjen; Vissenberg, Kris

    2015-01-01

    Plant roots fulfill important functions as they serve in water and nutrient uptake, provide anchorage of the plant body in the soil and in some species form the site of symbiotic interactions with soil-living biota. Root hairs, tubular-shaped outgrowths of specific epidermal cells, significantly increase the root’s surface area and aid in these processes. In this review we focus on the molecular mechanisms that determine the hair and non-hair cell fate of epidermal cells and that define the site on the epidermal cell where the root hair will be initiated (=planar polarity determination). In the model plant Arabidopsis, trichoblast and atrichoblast cell fate results from intra- and intercellular position-dependent signaling and from complex feedback loops that ultimately regulate GL2 expressing and non-expressing cells. When epidermal cells reach the end of the root expansion zone, root hair promoting transcription factors dictate the establishment of polarity within epidermal cells followed by the selection of the root hair initiation site at the more basal part of the trichoblast. Molecular players in the abovementioned processes as well as the role of phytohormones are discussed, and open areas for future experiments are identified. PMID:26779192

  14. Planar Cell Polarity Signaling: Coordination of cellular orientation across tissues

    PubMed Central

    Singh, Jaskirat; Mlodzik, Marek

    2012-01-01

    Establishment of Planar Cell Polarity (PCP) in epithelia, in the plane of an epithelium, is an important feature of the development and homeostasis of most organs. Studies in different model organisms have contributed a wealth of information regarding the mechanisms that govern PCP regulation. Genetic studies in Drosophila have identified two signaling systems, the Fz/PCP and Fat/Dachsous system, which are both required for PCP establishment in many different tissues in a largely non-redundant manner. Recent advances in vertebrate PCP studies have added novel factors of PCP regulation and also new cellular features requiring PCP signaling input, including the positioning and orientation of the primary cilium of many epithelial cells. This review focuses mostly on several recent advances made in the Drosophila and vertebrate PCP field and integrates these within the existing PCP signaling framework. PMID:23066429

  15. Modelling polarization and conduction processes in poly(ethylene naphthalate)

    NASA Astrophysics Data System (ADS)

    Hoang, M.-Q.; Boudou, L.; Teyssedre, G.; Le Roy, S.

    2017-08-01

    Challenges in the field of solid organic insulators are linked to the development of more compact, reliable and eco-friendly systems where these materials are employed as dielectrics. One way to increase the reliability of such systems is to understand and model the behavior of these materials under thermo-electrical stress, in order to prevent any failure. Fluid charge transport models have been developed to predict the charge accumulation in such materials when submitted to an external stress, mostly electrical. However, these kind of models are not enough to predict the global behavior of the material, as most of these dielectrics are polar materials, subjected to a non-negligible dipolar response. This paper shows the first simulation results produced using a global charge transport model including polarization, and compares simulated to experimental current measurements. For moderate fields and temperatures, the model is able to reproduce the experimental results, qualitatively and quantitatively.

  16. Primary processes in sensory cells: current advances.

    PubMed

    Frings, Stephan

    2009-01-01

    In the course of evolution, the strong and unremitting selective pressure on sensory performance has driven the acuity of sensory organs to its physical limits. As a consequence, the study of primary sensory processes illustrates impressively how far a physiological function can be improved if the survival of a species depends on it. Sensory cells that detect single-photons, single molecules, mechanical motions on a nanometer scale, or incredibly small fluctuations of electromagnetic fields have fascinated physiologists for a long time. It is a great challenge to understand the primary sensory processes on a molecular level. This review points out some important recent developments in the search for primary processes in sensory cells that mediate touch perception, hearing, vision, taste, olfaction, as well as the analysis of light polarization and the orientation in the Earth's magnetic field. The data are screened for common transduction strategies and common transduction molecules, an aspect that may be helpful for researchers in the field.

  17. M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells.

    PubMed

    Cui, Jiajun; Xu, Wenhua; Chen, Jian; Li, Hui; Dai, Lu; Frank, Jacqueline A; Peng, Shaojun; Wang, Siying; Chen, Gang

    2017-03-28

    The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages.

  18. M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells

    PubMed Central

    Li, Hui; Dai, Lu; Frank, Jacqueline A.; Peng, Shaojun; Wang, Siying; Chen, Gang

    2017-01-01

    The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages. PMID:28423485

  19. Mechanochemical feedback underlies coexistence of qualitatively distinct cell polarity patterns within diverse cell populations.

    PubMed

    Park, JinSeok; Holmes, William R; Lee, Sung Hoon; Kim, Hong-Nam; Kim, Deok-Ho; Kwak, Moon Kyu; Wang, Chiaochun Joanne; Edelstein-Keshet, Leah; Levchenko, Andre

    2017-07-11

    Cell polarization and directional cell migration can display random, persistent, and oscillatory dynamic patterns. However, it is not clear whether these polarity patterns can be explained by the same underlying regulatory mechanism. Here, we show that random, persistent, and oscillatory migration accompanied by polarization can simultaneously occur in populations of melanoma cells derived from tumors with different degrees of aggressiveness. We demonstrate that all of these patterns and the probabilities of their occurrence are quantitatively accounted for by a simple mechanism involving a spatially distributed, mechanochemical feedback coupling the dynamically changing extracellular matrix (ECM)-cell contacts to the activation of signaling downstream of the Rho-family small GTPases. This mechanism is supported by a predictive mathematical model and extensive experimental validation, and can explain previously reported results for diverse cell types. In melanoma, this mechanism also accounts for the effects of genetic and environmental perturbations, including mutations linked to invasive cell spread. The resulting mechanistic understanding of cell polarity quantitatively captures the relationship between population variability and phenotypic plasticity, with the potential to account for a wide variety of cell migration states in diverse pathological and physiological conditions.

  20. Design and implementation of the parallel processing system of multi-channel polarization images

    NASA Astrophysics Data System (ADS)

    Li, Zhi-yong; Huang, Qin-chao

    2013-08-01

    Compared with traditional optical intensity image processing, polarization images processing has two main problems. One is that the amount of data is larger. The other is that processing tasks is more complex. To resolve these problems, the parallel processing system of multi-channel polarization images is designed by the multi-DSP technique. It contains a communication control unit (CCU) and a data processing array (DPA). CCU controls communications inside and outside the system. Its logics are designed by a FPGA chip. DPA is made up of four Digital Signal Processor (DSP) chips, which are interlinked by the loose coupling method. DPA implements processing tasks including images registration and images synthesis by parallel processing methods. The polarization images parallel processing model is designed on multi levels including the system task, the algorithm and the operation. Its program is designed by the assemble language. While the polarization image resolution is 782x582 pixels, the pixel data length is 12 bits in the experiment. After it received 3 channels of polarization image simultaneously, this system implements parallel task to acquire the target polarization characteristics. Experimental results show that this system has good real-time and reliability. The processing time of images registration is 293.343ms while the registration accuracy achieves 0.5 pixel. The processing time of images synthesis is 3.199ms.

  1. VE-cadherin interacts with cell polarity protein Pals1 to regulate vascular lumen formation.

    PubMed

    Brinkmann, Benjamin F; Steinbacher, Tim; Hartmann, Christian; Kummer, Daniel; Pajonczyk, Denise; Mirzapourshafiyi, Fatemeh; Nakayama, Masanori; Weide, Thomas; Gerke, Volker; Ebnet, Klaus

    2016-09-15

    Blood vessel tubulogenesis requires the formation of stable cell-to-cell contacts and the establishment of apicobasal polarity of vascular endothelial cells. Cell polarity is regulated by highly conserved cell polarity protein complexes such as the Par3-aPKC-Par6 complex and the CRB3-Pals1-PATJ complex, which are expressed by many different cell types and regulate various aspects of cell polarity. Here we describe a functional interaction of VE-cadherin with the cell polarity protein Pals1. Pals1 directly interacts with VE-cadherin through a membrane-proximal motif in the cytoplasmic domain of VE-cadherin. VE-cadherin clusters Pals1 at cell-cell junctions. Mutating the Pals1-binding motif in VE-cadherin abrogates the ability of VE-cadherin to regulate apicobasal polarity and vascular lumen formation. In a similar way, deletion of the Par3-binding motif at the C-terminus of VE-cadherin impairs apicobasal polarity and vascular lumen formation. Our findings indicate that the biological activity of VE-cadherin in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins Pals1 and Par3.

  2. Global Observation of Substorm Growth Phase Processes in the Polar Caps

    NASA Technical Reports Server (NTRS)

    Brittnacher, M.; OFillingim, M. O.; Chua, D.; Wilber, M.; Parks, G. K.; Germany, G. A.; Spann, J. F.

    1998-01-01

    Global images of the polar cap region during the substorm growth phase by the Polar Ultraviolet Imager reveals evidence of the processes which are not completely explained by current models. In particular, it was found that size of the polar cap region increases during the growth phase even if the interplanetary magnetic field has no southward component. Three phenomena were observed to produce an increase in the size of the polar cap: (1) motion of the auroral oval to lower latitude, (2) thinning of the auroral oval, and (3) reduction of intense aurora[ precipitation in the polar region. Correlation of image intensities with in situ particle measurements from the FAST satellite are being conducted to study the three growth phase phenomena; and to help identify the source regions of the particles, the mechanisms involved in producing the auroral structures and what may be reducing the polar cap precipitation during the substorm growth phase.

  3. Modeling Yeast Cell Polarization Induced by Pheromone Gradients

    NASA Astrophysics Data System (ADS)

    Yi, Tau-Mu; Chen, Shanqin; Chou, Ching-Shan; Nie, Qing

    2007-07-01

    Yeast cells respond to spatial gradients of mating pheromones by polarizing and projecting up the gradient toward the source. It is thought that they employ a spatial sensing mechanism in which the cell compares the concentration of pheromone at different points on the cell surface and determines the maximum point, where the projection forms. Here we constructed the first spatial mathematical model of the yeast pheromone response that describes the dynamics of the heterotrimeric and Cdc42p G-protein cycles, which are linked in a cascade. Two key performance objectives of this system are (1) amplification—converting a shallow external gradient of ligand to a steep internal gradient of protein components and (2) tracking—following changes in gradient direction. We used simulations to investigate amplification mechanisms that allow tracking. We identified specific strategies for regulating the spatial dynamics of the protein components (i.e. their changing location in the cell) that would enable the cell to achieve both objectives.

  4. Tentative and transient natural killer cell polarization balances the requirements for discriminatory recognition and cytolytic efficacy.

    PubMed

    Sinai, Parisa; Roybal, Kole T; Wülfing, Christoph

    2010-11-01

    Natural killer (NK) cells are immune cells that lyse virally infected and tumor cells. Initially, their cytolytic capability is induced by cytokines. Subsequently, in their decision whether to kill a potential target cell, NK cells have to distinguish between small differences in the expression of ligands that report on the viral infection or transformation of the target. NK killing requires tight coupling to the target cell and extensive NK cell polarization. Here we discuss, often in contrast to the second cytolytic immune cell type, cytotoxic T cells, how NK cell polarization is shaped by three constraints of their activation. First, NK cell have to respond to cytokines: Different priming cytokines yield dramatically divergent NK cell polarization. Second, NK cells have to distinguish small differences in ligand expression: NK cell polarization is tentative, likely to allow discriminatory recognition close to the NK cell activation threshold. A critical contributor to the tentative nature of NK cell polarization may be poorly developed spatiotemporal organization of NK cell signaling. Third, NK cells have to kill effectively: NK cell polarization is transient, allowing for efficient killing by sequential interactions of a single NK cell with numerous target cells.

  5. Advantages and mechanisms of polarity and cell shape determination in Caulobacter crescentus

    PubMed Central

    Lawler, Melanie L.; Brun, Yves V.

    2007-01-01

    Summary The tremendous diversity of bacterial cell shapes and the targeting of proteins and macromolecular complexes to specific subcellular sites strongly suggest that cellular organization provides important advantages for bacteria in their environment. Key advances have been made in the understanding of the mechanism and function of polarity and cell shape by studying the aquatic bacterium Caulobacter crescentus, whose cell cycle progression involves the ordered synthesis of different polar structures, and culminates in the biosynthesis of a thin polar cell envelope extension called the stalk. Recent results indicate that one important function of polar development is to maximize cell attachment to surfaces and to improve nutrient uptake by non-motile and attached cells. Major progress has been made in understanding the regulatory network that coordinates polar development and morphogenesis, and the role of polar localization of regulatory proteins. PMID:17997127

  6. VE-cadherin interacts with cell polarity protein Pals1 to regulate vascular lumen formation

    PubMed Central

    Brinkmann, Benjamin F.; Steinbacher, Tim; Hartmann, Christian; Kummer, Daniel; Pajonczyk, Denise; Mirzapourshafiyi, Fatemeh; Nakayama, Masanori; Weide, Thomas; Gerke, Volker; Ebnet, Klaus

    2016-01-01

    Blood vessel tubulogenesis requires the formation of stable cell-to-cell contacts and the establishment of apicobasal polarity of vascular endothelial cells. Cell polarity is regulated by highly conserved cell polarity protein complexes such as the Par3-aPKC-Par6 complex and the CRB3-Pals1-PATJ complex, which are expressed by many different cell types and regulate various aspects of cell polarity. Here we describe a functional interaction of VE-cadherin with the cell polarity protein Pals1. Pals1 directly interacts with VE-cadherin through a membrane-proximal motif in the cytoplasmic domain of VE-cadherin. VE-cadherin clusters Pals1 at cell–cell junctions. Mutating the Pals1-binding motif in VE-cadherin abrogates the ability of VE-cadherin to regulate apicobasal polarity and vascular lumen formation. In a similar way, deletion of the Par3-binding motif at the C-terminus of VE-cadherin impairs apicobasal polarity and vascular lumen formation. Our findings indicate that the biological activity of VE-cadherin in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins Pals1 and Par3. PMID:27466317

  7. Planar cell polarity signalling couples cell division and morphogenesis during neurulation

    PubMed Central

    Ciruna, Brian; Jenny, Andreas; Lee, Diana; Mlodzik, Marek; Schier, Alexander F.

    2006-01-01

    Environmental and genetic aberrations lead to neural tube closure defects (NTDs) in 1 in every 1000 births1. Mouse and frog models for these birth defects have suggested that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other components of planar cell polarity (PCP) signalling control neurulation by promoting the convergence of neural progenitors to the midline2-8. Here we report a novel role for PCP signalling during neurulation in zebrafish. We demonstrate that non-canonical Wnt/PCP signalling polarizes neural progenitors along the anterior-posterior axis. This polarity is transiently lost during cell division in the neural keel but is re-established as daughter cells reintegrate into the neuroepithelium. Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the polarization of neural keel cells, disrupts re-intercalation of daughter cells into the neuroepithelium, and results in ectopic neural progenitor accumulations and NTDs. Remarkably, blocking cell division leads to rescue of trilobite neural tube morphogenesis despite persistent defects in convergence and extension. These results reveal a role for PCP signalling in coupling cell division and morphogenesis at neurulation and suggest a novel mechanism underlying NTDs. PMID:16407953

  8. Establishing and maintaining cell polarity with mRNA localization in Drosophila.

    PubMed

    Barr, Justinn; Yakovlev, Konstantin V; Shidlovskii, Yulii; Schedl, Paul

    2016-03-01

    How cell polarity is established and maintained is an important question in diverse biological contexts. Molecular mechanisms used to localize polarity proteins to distinct domains are likely context-dependent and provide a feedback loop in order to maintain polarity. One such mechanism is the localized translation of mRNAs encoding polarity proteins, which will be the focus of this review and may play a more important role in the establishment and maintenance of polarity than is currently known. Localized translation of mRNAs encoding polarity proteins can be used to establish polarity in response to an external signal, and to maintain polarity by local production of polarity determinants. The importance of this mechanism is illustrated by recent findings, including orb2-dependent localized translation of aPKC mRNA at the apical end of elongating spermatid tails in the Drosophila testis, and the apical localization of stardust A mRNA in Drosophila follicle and embryonic epithelia.

  9. Establishment of planar cell polarity is coupled to regional cell cycle exit and cell differentiation in the mouse utricle

    PubMed Central

    Yang, Xiaoyu; Qian, Xiaoqing; Ma, Rui; Wang, Xinwei; Yang, Juanmei; Luo, Wenwei; Chen, Ping; Chi, Fanglu; Ren, Dongdong

    2017-01-01

    Sensory hair cells are coordinately oriented within each inner ear sensory organ to exhibit a particular form of planar cell polarity (PCP) necessary for mechanotransduction. However, the developmental events associated with establishing PCP in the vestibule are unclear, hindering data interpretation and employment of the vestibule for PCP studies. Herein, we investigated PCP of the mouse vestibular organs. We further characterised cell cycle exit, cell differentiation, and PCP establishment in the utricle. We found that hair cells formed first in the striolar and medial extrastriolar (MES) regions of the utricle at embryonic day 11.5 (E11.5), while cells in the lateral extrastriolar region (LES) mostly formed at E13.5. Cell differentiation was initiated in the striolar region, which expanded first toward the MES, then to the LES by E15.5. The polarity of hair cells was established at birth along a putative line of polarity reversal (LPR), lateral to the striolar region. Core PCP protein Vangl2 emerged in the cell boundaries since E11.5, while cell intrinsic polarity protein Gαi3 appeared at E12.5, then polarized to the bare zone of individual hair cell at E13.5. These findings provide a blueprint of the developmental events associated with establishing PCP in the utricle. PMID:28230212

  10. Complex polar machinery required for proper chromosome segregation in vegetative and sporulating cells of Bacillus subtilis

    PubMed Central

    Kloosterman, Tomas G.; Lenarcic, Rok; Willis, Clare R.; Roberts, David M.; Hamoen, Leendert W.; Errington, Jeff

    2016-01-01

    Summary Chromosome segregation is an essential process of cell multiplication. In prokaryotes, segregation starts with the newly replicated sister origins of replication, oriCs, which move apart to defined positions in the cell. We have developed a genetic screen to identify mutants defective in placement of oriC during spore development in the Gram‐positive bacterium Bacillus subtilis. In addition to the previously identified proteins Soj and DivIVA, our screen identified several new factors involved in polar recruitment of oriC: a reported regulator of competence ComN, and the regulators of division site selection MinD and MinJ. Previous work implicated Soj as an important regulator of oriC positioning in the cell. Our results suggest a model in which the DivIVA‐interacting proteins ComN and MinJ recruit MinD to the cell pole, and that these proteins work upstream of Soj to enable oriC placement. We show that these proteins form a polar complex, which acts in parallel with but distinct from the sporulation‐specific RacA pathway of oriC placement, and also functions during vegetative growth. Our study further shows that MinD has two distinct cell cycle roles, in cell division and chromosome segregation, and highlights that cell probably use multiple parallel mechanisms to ensure accurate chromosome segregation. PMID:27059541

  11. Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division

    PubMed Central

    Jordan, Shawn N.; Davies, Tim; Zhuravlev, Yelena; Dumont, Julien; Shirasu-Hiza, Mimi

    2016-01-01

    Cytokinesis, the physical division of one cell into two, is thought to be fundamentally similar in most animal cell divisions and driven by the constriction of a contractile ring positioned and controlled solely by the mitotic spindle. During asymmetric cell divisions, the core polarity machinery (partitioning defective [PAR] proteins) controls the unequal inheritance of key cell fate determinants. Here, we show that in asymmetrically dividing Caenorhabditis elegans embryos, the cortical PAR proteins (including the small guanosine triphosphatase CDC-42) have an active role in regulating recruitment of a critical component of the contractile ring, filamentous actin (F-actin). We found that the cortical PAR proteins are required for the retention of anillin and septin in the anterior pole, which are cytokinesis proteins that our genetic data suggest act as inhibitors of F-actin at the contractile ring. Collectively, our results suggest that the cortical PAR proteins coordinate the establishment of cell polarity with the physical process of cytokinesis during asymmetric cell division to ensure the fidelity of daughter cell formation. PMID:26728855

  12. On the low-frequency electrical polarization of bacterial cells in sands

    NASA Astrophysics Data System (ADS)

    Ntarlagiannis, Dimitrios; Yee, Nathan; Slater, Lee

    2005-12-01

    We performed electrical measurements on sands flushed with bacterial suspensions of varying concentration. The first experiment was conducted with Shewanella putrefaciens (biomass 0-0.5 mg/L) and the second with Escherichia coli (biomass 0-42 mg/L). We measured a biomass-dependent low-frequency (10 Hz) polarization. At cell density <12 mg/L polarization decreased (up to 60 %) relative to before introduction of cells; the decrease was greater when the sand was artificially Fe-coated to enhance the affinity of cells to the mineral surface. At cell density >12 mg/L polarization increased (up to 15%). We attribute the decrease in polarization at low cell density to alteration of the mineral-fluid interface due to mineral-cell interactions. The polarization enhancement at higher cell density is possibly a pore throat mechanism resulting from decreased ionic mobility and/or electron transfer due to cell accumulation in pores.

  13. Engineering a polarity-sensitive biosensor for time-lapse imaging of apoptotic processes and degeneration

    PubMed Central

    Kim, Yujin E; Chen, Jeannie; Chan, Jonah R; Langen, Ralf

    2010-01-01

    Apoptosis is of central importance to many areas of biological research, but there is a lack of methods that permit continuous monitoring of apoptosis or cell viability in a nontoxic and noninvasive manner. Here we report the development of a tool applicable to live-cell imaging that facilitates the visualization of real-time apoptotic changes without perturbing the cellular environment. We designed a polarity-sensitive annexin-based biosensor (pSIVA) with switchable fluorescence states, which allows detection only when bound to apoptotic cells. Using pSIVA with live-cell imaging, we observed dynamic local changes in individual rat neurons during degeneration in vitro and in vivo. Furthermore, we observed that pSIVA binding was reversible and clearly defined the critical period for neurons to be rescued. We anticipate pSIVA can be widely applied to address questions concerning spatiotemporal events in apoptotic processes, its reversibility and the general viability of cells in culture. PMID:19966809

  14. Bipolar Plasma Membrane Distribution of Phosphoinositides and Their Requirement for Auxin-Mediated Cell Polarity and Patterning in Arabidopsis.

    PubMed

    Tejos, Ricardo; Sauer, Michael; Vanneste, Steffen; Palacios-Gomez, Miriam; Li, Hongjiang; Heilmann, Mareike; van Wijk, Ringo; Vermeer, Joop E M; Heilmann, Ingo; Munnik, Teun; Friml, Jiří

    2014-05-01

    Cell polarity manifested by asymmetric distribution of cargoes, such as receptors and transporters, within the plasma membrane (PM) is crucial for essential functions in multicellular organisms. In plants, cell polarity (re)establishment is intimately linked to patterning processes. Despite the importance of cell polarity, its underlying mechanisms are still largely unknown, including the definition and distinctiveness of the polar domains within the PM. Here, we show in Arabidopsis thaliana that the signaling membrane components, the phosphoinositides phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] as well as PtdIns4P 5-kinases mediating their interconversion, are specifically enriched at apical and basal polar plasma membrane domains. The PtdIns4P 5-kinases PIP5K1 and PIP5K2 are redundantly required for polar localization of specifically apical and basal cargoes, such as PIN-FORMED transporters for the plant hormone auxin. As a consequence of the polarity defects, instructive auxin gradients as well as embryonic and postembryonic patterning are severely compromised. Furthermore, auxin itself regulates PIP5K transcription and PtdIns4P and PtdIns(4,5)P2 levels, in particular their association with polar PM domains. Our results provide insight into the polar domain-delineating mechanisms in plant cells that depend on apical and basal distribution of membrane lipids and are essential for embryonic and postembryonic patterning. © 2014 American Society of Plant Biologists. All rights reserved.

  15. Diesel exhaust particles induce aberrant alveolar epithelial directed cell movement by disruption of polarity mechanisms.

    PubMed

    LaGier, Adriana J; Manzo, Nicholas D; Dye, Janice A

    2013-01-01

    Disruption of the respiratory epithelium contributes to the progression of a variety of respiratory diseases that are aggravated by exposure to air pollutants, specifically traffic-based pollutants such as diesel exhaust particles (DEP). Recognizing that lung repair following injury requires efficient and directed alveolar epithelial cell migration, this study's goal was to understand the mechanisms underlying alveolar epithelial cells response to DEP, particularly when exposure is accompanied with comorbid lung injury. Separate mechanistic steps of directed migration were investigated in confluent murine LA-4 cells exposed to noncytotoxic concentrations (0-100 μg/cm(2)) of either automobile-emitted diesel exhaust particles (DEP(A)) or carbon black (CB) particles. A scratch wound model ascertained how DEP(A) exposure affected directional cell migration and BCECF ratio fluorimetry-monitored intracellular pH (pHi). Cells were immunostained with giantin to assess cell polarity, and with paxillin to assess focal cell adhesions. Cells were immunoblotted for ezrin/radixin/moesin (ERM) to assess cytoskeletal anchoring. Data demonstrate herein that exposure of LA-4 cells to DEP(A) (but not CB) resulted in delayed directional cell migration, impaired de-adhesion of the trailing edge cell processes, disrupted regulation of pHi, and altered Golgi polarity of leading edge cells, along with modified focal adhesions and reduced ERM levels, indicative of decreased cytoskeletal anchoring. The ability of DEP(A) to disrupt directed cell migration at multiple levels suggests that signaling pathways such as ERM/Rho are critical for transduction of ion transport signals into cytoskeletal arrangement responses. These results provide insights into the mechanisms by which chronic exposure to traffic-based emissions may result in decrements in lung capacity.

  16. LFA-1 Engagement Triggers T Cell Polarization at the HIV-1 Virological Synapse.

    PubMed

    Starling, Shimona; Jolly, Clare

    2016-11-01

    HIV-1 efficiently disseminates by cell-cell spread at intercellular contacts called virological synapses (VS), where the virus preferentially assembles and buds. Cell-cell contact triggers active polarization of organelles and viral proteins within infected cells to the contact site to support efficient VS formation and HIV-1 spread; critically, however, which cell surface protein triggers contact-induced polarization at the VS remains unclear. Additionally, the mechanism by which the HIV-1 envelope glycoprotein (Env) is recruited to the VS remains ill defined. Here, we use a reductionist bead-coupled antibody assay as a model of the VS and show that cross-linking the integrin LFA-1 alone is sufficient to induce active T cell polarization and recruitment of the microtubule organizing center (MTOC) in HIV-1-infected cells. Mutant cell lines coupled with inhibitors demonstrated that LFA-1-induced polarization was dependent on the T cell kinase ZAP70. Notably, immunofluorescent staining of viral proteins revealed an accumulation of surface Env at sites of LFA-1 engagement, with intracellular Env localized to a Golgi compartment proximal to the polarized MTOC. Furthermore, blocking LFA-1-induced MTOC polarization through ZAP70 inhibition prevented intracellular Env polarization. Taken together, these data reveal that LFA-1 is a key determinant in inducing dynamic T cell remodeling to the VS and suggest a model in which LFA-1 engagement triggers active polarization of the MTOC and the associated Env-containing secretory apparatus to sites of cell-cell contact to support polarized viral assembly and egress for efficient cell-cell spread. HIV-1 causes AIDS by spreading within immune cells and depletion of CD4 T lymphocytes. Rapid spread between these cells occurs by highly efficient cell-cell transmission that takes place at virological synapses (VS). VS are characterized by striking T cell remodeling that is spatially associated with polarized virus assembly and budding

  17. LFA-1 Engagement Triggers T Cell Polarization at the HIV-1 Virological Synapse

    PubMed Central

    Starling, Shimona

    2016-01-01

    ABSTRACT HIV-1 efficiently disseminates by cell-cell spread at intercellular contacts called virological synapses (VS), where the virus preferentially assembles and buds. Cell-cell contact triggers active polarization of organelles and viral proteins within infected cells to the contact site to support efficient VS formation and HIV-1 spread; critically, however, which cell surface protein triggers contact-induced polarization at the VS remains unclear. Additionally, the mechanism by which the HIV-1 envelope glycoprotein (Env) is recruited to the VS remains ill defined. Here, we use a reductionist bead-coupled antibody assay as a model of the VS and show that cross-linking the integrin LFA-1 alone is sufficient to induce active T cell polarization and recruitment of the microtubule organizing center (MTOC) in HIV-1-infected cells. Mutant cell lines coupled with inhibitors demonstrated that LFA-1-induced polarization was dependent on the T cell kinase ZAP70. Notably, immunofluorescent staining of viral proteins revealed an accumulation of surface Env at sites of LFA-1 engagement, with intracellular Env localized to a Golgi compartment proximal to the polarized MTOC. Furthermore, blocking LFA-1-induced MTOC polarization through ZAP70 inhibition prevented intracellular Env polarization. Taken together, these data reveal that LFA-1 is a key determinant in inducing dynamic T cell remodeling to the VS and suggest a model in which LFA-1 engagement triggers active polarization of the MTOC and the associated Env-containing secretory apparatus to sites of cell-cell contact to support polarized viral assembly and egress for efficient cell-cell spread. IMPORTANCE HIV-1 causes AIDS by spreading within immune cells and depletion of CD4 T lymphocytes. Rapid spread between these cells occurs by highly efficient cell-cell transmission that takes place at virological synapses (VS). VS are characterized by striking T cell remodeling that is spatially associated with polarized virus

  18. The Influence of Local Geometric Effects on Mars Polar Processes

    NASA Technical Reports Server (NTRS)

    Hecht, M. H.

    2005-01-01

    Using simple, qualitative heat balance models, this paper addresses textures and structures that will result from the evolution of volatile layers by accretion and by ablation. Such phenomena may have global implications that are not apparent when only flat or sloped surfaces are modeled. In general, structures such as mounds or depressions formed out of volatile materials will evolve in shape such that the growth or retreat of any particular surface will be maximized. It can be shown that the local radius of curvature is proportional to the growth or retreat rate. For example, icy surfaces will tend to form facets that face the dominant sun direction. Two such cases are evaluated: a) Features associated with condensation of volatiles, include cold-trapping and redistribution, such as the concentration of frost around the Viking 2 lander [1]. Here I will focus on textures that likely result from the formation of seasonal CO2 deposits. b) Features associated with sublimation of volatiles, such as those described by Ingersoll et. al. [2] result in textured surfaces that affect both the apparent emissivity and albedo. Similar calculations have been performed with respect to the "Swiss cheese" features on the South Polar Cap [3]. Here, I evaluate the likely sublimation rates from optimal ice scarp structures and their implications for the long-term evolution of the polar caps and formation of layered terrain.

  19. Non-invasive imaging of cellulose microfibril orientation within plant cell walls by polarized Raman microspectroscopy.

    PubMed

    Sun, Lan; Singh, Seema; Joo, Michael; Vega-Sanchez, Miguel; Ronald, Pamela; Simmons, Blake A; Adams, Paul; Auer, Manfred

    2016-01-01

    Cellulose microfibrils represent the major scaffold of plant cell walls. Different packing and orientation of the microfibrils at the microscopic scale determines the macroscopic properties of cell walls and thus affect their functions with a profound effect on plant survival. We developed a polarized Raman microspectroscopic method to determine cellulose microfibril orientation within rice plant cell walls. Employing an array of point measurements as well as area imaging and subsequent Matlab-assisted data processing, we were able to characterize the distribution of cellulose microfibril orientation in terms of director angle and anisotropy magnitude. Using this approach we detected differences between wild type rice plants and the rice brittle culm mutant, which shows a more disordered cellulose microfibril arrangement, and differences between different tissues of a wild type rice plant. This novel non-invasive Raman imaging approach allows for quantitative assessment of cellulose fiber orientation in cell walls of herbaceous plants, an important advancement in cell wall characterization.

  20. Dystroglycan loss disrupts polarity and beta-casein induction inmammary epithelial cells by perturbing laminin anchoring

    SciTech Connect

    Weir, M. Lynn; Oppizzi, Maria Luisa; Henry, Michael D.; Onishi,Akiko; Campbell, Kevin P.; Bissell, Mina J.; Muschler, John L.

    2006-02-17

    Precise contact between epithelial cells and their underlying basement membrane is critical to the maintenance of tissue architecture and function. To understand the role that the laminin receptor dystroglycan (DG) plays in these processes, we assayed cell responses to laminin-111 following conditional ablation of DG expression in cultured mammary epithelial cells (MECs). Strikingly, DG loss disrupted laminin-111-induced polarity and {beta}-casein production, and abolished laminin assembly at the step of laminin binding to the cell surface. DG re-expression restored these deficiencies. Investigations of mechanism revealed that DG cytoplasmic sequences were not necessary for laminin assembly and signaling, and only when the entire mucin domain of extracellular DG was deleted did laminin assembly not occur. These results demonstrate that DG is essential as a laminin-111 co-receptor in MECs that functions by mediating laminin anchoring to the cell surface, a process that allows laminin polymerization, tissue polarity, and {beta}-casein induction. The observed loss of laminin-111 assembly and signaling in DG-/-MECs provides insights into the signaling changes occurring in breast carcinomas and other cancers, where DG's laminin-binding function is frequently defective.

  1. Gamma-ray polarization of the synchrotron self-compton process from a highly relativistic jet

    SciTech Connect

    Chang, Zhe; Lin, Hai-Nan

    2014-11-01

    The high polarization observed in the prompt phase of some gamma-ray bursts invites extensive study of the emission mechanism. In this paper, we investigate the polarization properties of the synchrotron self-Compton (SSC) process from a highly relativistic jet. A magnetic-dominated, baryon-loaded jet ejected from the central engine travels with a large Lorentz factor. Shells with slightly different velocities collide with each other and produce shocks. The shocks accelerate electrons to a power-law distribution and, at the same time, magnify the magnetic field. Electrons move in the magnetic field and produce synchrotron photons. Synchrotron photons suffer from the Compton scattering (CS) process and then are detected by an observer located slightly off-axis. We analytically derive the formulae of photon polarization in the SSC process in two magnetic configurations: a magnetic field in the shock plane and perpendicular to the shock plane. We show that photons induced by the SSC process can be highly polarized, with the maximum polarization Π ∼ 24% in the energy band [0.5, 5] MeV. The polarization depends on the viewing angles, peaking in the plane perpendicular to the magnetic field. In the energy band [0.05, 0.5] MeV, in which most γ-ray polarimeters are active, the polarization is about twice that in the Thomson limit, reaching Π ∼ 20%. This implies that the Klein-Nishina effect, which is often neglected in the literature, should be carefully considered.

  2. Gamma-Ray Polarization of the Synchrotron Self-compton Process from a Highly Relativistic Jet

    NASA Astrophysics Data System (ADS)

    Chang, Zhe; Lin, Hai-Nan

    2014-11-01

    The high polarization observed in the prompt phase of some gamma-ray bursts invites extensive study of the emission mechanism. In this paper, we investigate the polarization properties of the synchrotron self-Compton (SSC) process from a highly relativistic jet. A magnetic-dominated, baryon-loaded jet ejected from the central engine travels with a large Lorentz factor. Shells with slightly different velocities collide with each other and produce shocks. The shocks accelerate electrons to a power-law distribution and, at the same time, magnify the magnetic field. Electrons move in the magnetic field and produce synchrotron photons. Synchrotron photons suffer from the Compton scattering (CS) process and then are detected by an observer located slightly off-axis. We analytically derive the formulae of photon polarization in the SSC process in two magnetic configurations: a magnetic field in the shock plane and perpendicular to the shock plane. We show that photons induced by the SSC process can be highly polarized, with the maximum polarization Π ~ 24% in the energy band [0.5, 5] MeV. The polarization depends on the viewing angles, peaking in the plane perpendicular to the magnetic field. In the energy band [0.05, 0.5] MeV, in which most γ-ray polarimeters are active, the polarization is about twice that in the Thomson limit, reaching Π ~ 20%. This implies that the Klein-Nishina effect, which is often neglected in the literature, should be carefully considered.

  3. Polarity in plant asymmetric cell division: Division orientation and cell fate differentiation.

    PubMed

    Shao, Wanchen; Dong, Juan

    2016-11-01

    Asymmetric cell division (ACD) is universally required for the development of multicellular organisms. Unlike animal cells, plant cells have a rigid cellulosic extracellular matrix, the cell wall, which provides physical support and forms communication routes. This fundamental difference leads to some unique mechanisms in plants for generating asymmetries during cell division. However, plants also utilize intrinsically polarized proteins to regulate asymmetric signaling and cell division, a strategy similar to the differentiation mechanism found in animals. Current progress suggests that common regulatory modes, i.e. protein spontaneous clustering and cytoskeleton reorganization, underlie protein polarization in both animal and plant cells. Despite these commonalities, it is important to note that intrinsic mechanisms in plants are heavily influenced by extrinsic cues. To control physical asymmetry in cell division, although our understanding is fragmentary thus far, plants might have evolved novel polarization strategies to orientate cell division plane. Recent studies also suggest that the phytohormone auxin, one of the most pivotal small molecules in plant development, regulates ACD in plants. Copyright © 2016. Published by Elsevier Inc.

  4. Polarity in plant asymmetric cell division: Division orientation and cell fate differentiation

    PubMed Central

    Shao, Wanchen; Dong, Juan

    2017-01-01

    Asymmetric cell division (ACD) is universally required for the development of multicellular organisms. Unlike animal cells, plant cells have a rigid cellulosic extracellular matrix, the cell wall, which provides physical support and forms communication routes. This fundamental difference leads to some unique mechanisms in plants for generating asymmetries during cell division. However, plants also utilize intrinsically polarized proteins to regulate asymmetric signaling and cell division, a strategy similar to the differentiation mechanism found in animals. Current progress suggests that common regulatory modes, i.e. protein spontaneous clustering and cytoskeleton reorganization, underlie protein polarization in both animal and plant cells. Despite these commonalities, it is important to note that intrinsic mechanisms in plants are heavily influenced by extrinsic cues. To control physical asymmetry in cell division, although our understanding is fragmentary thus far, plants might have evolved novel polarization strategies to orientate cell division plane. Recent studies also suggest that the phytohormone auxin, one of the most pivotal small molecules in plant development, regulates ACD in plants. PMID:27475487

  5. Effect of dust particle polarization on scattering processes in complex plasmas

    SciTech Connect

    Kodanova, S. K.; Ramazanov, T. S.; Bastykova, N. Kh.; Moldabekov, Zh. A.

    2015-06-15

    Screened interaction potentials in dusty plasmas taking into account the polarization of dust particles have been obtained. On the basis of screened potentials scattering processes for ion-dust particle and dust particle-dust particle pairs have been studied. In particular, the scattering cross section is considered. The scattering processes for which the dust grain polarization is unimportant have been found. The effect of zero angle dust particle-dust particle scattering is predicted.

  6. Self-organized spatiotemporal patterns of PIP3 and PTEN during spontaneous cell polarization

    NASA Astrophysics Data System (ADS)

    Knoch, Fabian; Tarantola, Marco; Rappel, Wouter-Jan; Bodenschatz, Eberhard

    2014-03-01

    During spontaneous cell polarization of Dictyostelium discoideum cells, PIP3 (phosphatidylinositol (3,4,5)-triphoshpate) and PTEN (phosphatase tensin homolog) have been identified as key signaling molecules, which govern the process of polarization in a self-organized manner. Gerisch et al. have shown that randomly triggered excitable PIP3 waves regulate the anti-correlated PTEN concentration. Here we show that this requires a switch-like dynamics of the overall membrane bound PTEN concentration in combination with two species of PTEN differing in their dephosphorylation rates. A quantitative modeling with a coupled reaction-diffusion system shows excellent agreement with experimental results and predicts a ratio σ of dephosphorylation rates acting on PIP3 of σ ~ 80 - 100. Our quantitative analysis suggests that surface-attached cell membrane spanning PIP3 waves are necessary for resetting the global actin network. This is evidenced by the experimentally observed delay between polarization-cycles also quantitatively captured by our analysis. Max Planck Society and Center for Theoretical Biological Physics.

  7. Apical myosin XI anticipates F-actin during polarized growth of Physcomitrella patens cells.

    PubMed

    Furt, Fabienne; Liu, Yen-Chun; Bibeau, Jeffrey P; Tüzel, Erkan; Vidali, Luis

    2013-02-01

    Tip growth is essential for land colonization by bryophytes, plant sexual reproduction and water and nutrient uptake. Because this specialized form of polarized cell growth requires both a dynamic actin cytoskeleton and active secretion, it has been proposed that the F-actin-associated motor myosin XI is essential for this process. Nevertheless, a spatial and temporal relationship between myosin XI and F-actin during tip growth is not known in any plant cell. Here, we use the highly polarized cells of the moss Physcomitrella patens to show that myosin XI and F-actin localize, in vivo, at the same apical domain and that both signals fluctuate. Surprisingly, phase analysis shows that increase in myosin XI anticipates that of F-actin; in contrast, myosin XI levels at the tip fluctuate in identical phase with a vesicle marker. Pharmacological analysis using a low concentration of the actin polymerization inhibitor latrunculin B showed that the F-actin at the tip can be significantly diminished while myosin XI remains elevated in this region, suggesting that a mechanism exists to cluster myosin XI-associated structures at the cell's apex. In addition, this approach uncovered a mechanism for actin polymerization-dependent motility in the moss cytoplasm, where myosin XI-associated structures seem to anticipate and organize the actin polymerization machinery. From our results, we inferred a model where the interaction between myosin XI-associated vesicular structures and F-actin polymerization-driven motility function at the cell's apex to maintain polarized cell growth. We hypothesize this is a general mechanism for the participation of myosin XI and F-actin in tip growing cells. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

  8. Shaping the mammalian auditory sensory organ by the planar cell polarity pathway

    PubMed Central

    Kelly, Michael; Chen, Ping

    2014-01-01

    The human ear is capable of processing sound with a remarkable resolution over a wide range of intensity and frequency. This ability depends largely on the extraordinary feats of the hearing organ, the organ of Corti and its sensory hair cells. The organ of Corti consists of precisely patterned rows of sensory hair cells and supporting cells along the length of the snail-shaped cochlear duct. On the apical surface of each hair cell, several rows of actin-containing protrusions, known as stereocilia, form a “V”-shaped staircase. The vertices of all the “V”-shaped stereocilia point away from the center of the cochlea. The uniform orientation of stereocilia in the organ of Corti manifests a distinctive form of polarity known as planar cell polarity (PCP). Functionally, the direction of stereociliary bundle deflection controls the mechanical channels located in the stereocilia for auditory transduction. In addition, hair cells are tonotopically organized along the length of the cochlea. Thus, the uniform orientation of stereociliary bundles along the length of the cochlea is critical for effective mechanotransduction and for frequency selection. Here we summarize the morphological and molecular events that bestow the structural characteristics of the mammalian hearing organ, the growth of the snail-shaped cochlear duct and the establishment of PCP in the organ of Corti. The PCP of the sensory organs in the vestibule of the inner ear will also be described briefly. PMID:17891715

  9. A two-step Notch-dependant mechanism controls the selection of the polar cell pair in Drosophila oogenesis.

    PubMed

    Vachias, Caroline; Couderc, Jean-Louis; Grammont, Muriel

    2010-08-01

    Organisers control the patterning and growth of many tissues and organs. Correctly regulating the size of these organisers is crucial for proper differentiation to occur. Organiser activity in the epithelium of the Drosophila ovarian follicle resides in a pair of cells called polar cells. It is known that these two cells are selected from a cluster of equivalent cells. However, the mechanisms responsible for this selection are still unclear. Here, we present evidence that the selection of the two cells is not random but, by contrast, depends on an atypical two-step Notch-dependent mechanism. We show that this sequential process begins when one cell becomes refractory to Notch activation and is selected as the initial polar cell. This cell then produces a Delta signal that induces a high level of Notch activation in one other cell within the cluster. This Notch activity prevents elimination by apoptosis, allowing its selection as the second polar cell. Therefore, the mechanism used to select precisely two cells from among an equivalence group involves an inductive Delta signal that originates from one cell, itself unable to respond to Notch activation, and results in one other cell being selected to adopt the same fate. Given its properties, this two-step Notch-dependent mechanism represents a novel aspect of Notch action.

  10. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

    PubMed

    Sun, Miao; Asghar, Suwaiba Z; Zhang, Huaye

    2016-09-01

    The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb

    PubMed Central

    Sun, Miao; Asghar, Suwaiba Z.; Zhang, Huaye

    2016-01-01

    The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer’s disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. PMID:27072891

  12. Rho GTPases and Regulation of Cell Migration and Polarization in Human Corneal Epithelial Cells

    PubMed Central

    Hou, Aihua; Toh, Li Xian; Gan, Kah Hui; Lee, Khee Jin Ryan; Manser, Edward; Tong, Louis

    2013-01-01

    Purpose Epithelial cell migration is required for regeneration of tissues and can be defective in a number of ocular surface diseases. This study aimed to determine the expression pattern of Rho family small G-proteins in human corneal epithelial cells to test their requirement in directional cell migration. Methods Rho family small G-protein expression was assessed by reverse transcription-polymerase chain reaction. Dominant-inhibitory constructs encoding Rho proteins or Rho protein targeting small interfering RNA were transfected into human corneal epithelial large T antigen cells, and wound closure rate were evaluated by scratch wounding assay, and a complementary non-traumatic cell migration assay. Immunofluorescence staining was performed to study cell polarization and to assess Cdc42 downstream effector. Results Cdc42, Chp, Rac1, RhoA, TC10 and TCL were expressed in human corneal epithelial cells. Among them, Cdc42 and TCL were found to significantly affect cell migration in monolayer scratch assays. These results were confirmed through the use of validated siRNAs directed to Cdc42 and TCL. Scramble siRNA transfected cells had high percentage of polarized cells than Cdc42 or TCL siRNA transfected cells at the wound edge. We showed that the Cdc42-specific effector p21-activated kinase 4 localized predominantly to cell-cell junctions in cell monolayers, but failed to translocate to the leading edge in Cdc42 siRNA transfected cells after monolayer wounding. Conclusion Rho proteins expressed in cultured human corneal epithelial cells, and Cdc42, TCL facilitate two-dimensional cell migration in-vitro. Although silencing of Cdc42 and TCL did not noticeably affect the appearance of cell adhesions at the leading edge, the slower migration of these cells indicates both GTP-binding proteins play important roles in promoting cell movement of human corneal epithelial cells. PMID:24130842

  13. Photon spectrum and polarization for high conversion coefficient in the Compton backscattering process

    NASA Astrophysics Data System (ADS)

    Potylitsyn, A. P.; Kolchuzhkin, A. M.; Strikhanov, M. N.; Strokov, S. A.

    2017-07-01

    This study looks to simulate the nonlinear Compton backscattering (CBS) process based on the Monte Carlo technique for the conversion coefficient Kc ⩾ 1 , which can be considered as the average number of photons emitted by each electron. The characteristics of the nonlinear CBS process simulated in this work are as follows: the number of absorbed photons of a laser, the distance in the laser pulse in which the electron passes between two collisions, the energy and the polarization of the emitted photon in each collision, and the polarization of the electron before and after collision. The developed approach allows us to find the spectra and polarization characteristics of the final electrons and photons. When Kc > 1 , the spin-flip processes need to be considered for a correct simulation of the polarization of the final photons and electrons for energies typical of a γ- γ collider.

  14. Wnt Signals Can Function as Positional Cues in Establishing Cell Polarity

    PubMed Central

    Goldstein, Bob; Takeshita, Hisako; Mizumoto, Kota; Sawa, Hitoshi

    2008-01-01

    Summary Wnt signaling plays important roles in cell polarization in diverse organisms, and loss of cell polarity is an early event in tumorigenesis caused by mutations in Wnt pathway genes. Despite this, the precise roles of Wnt proteins in cell polarization have remained elusive. In no organism has it been shown that the asymmetric position of a Wnt signal is essential to establishing a cell’s polarity. Attempts to test this by ubiquitous expression of Wnt genes have suggested that Wnt signals might act only as permissive factors in cell polarization. Here we find, using cell manipulations and ectopic gene expression in C. elegans, that the position from which Wnt signals are presented can determine the polarity of both embryonic and postembryonic cells. Furthermore, the position from which a Wnt signal is presented can determine the polarity of Frizzled receptor localization, suggesting that the polarizing effect of Wnt is likely to be direct. These results demonstrate that Wnt proteins can function as positional cues in establishing cell polarity. PMID:16516841

  15. Mechanistic framework for establishment, maintenance, and alteration of cell polarity in plants.

    PubMed

    Dhonukshe, Pankaj

    2012-01-01

    Cell polarity establishment, maintenance, and alteration are central to the developmental and response programs of nearly all organisms and are often implicated in abnormalities ranging from patterning defects to cancer. By residing at the distinct plasma membrane domains polar cargoes mark the identities of those domains, and execute localized functions. Polar cargoes are recruited to the specialized membrane domains by directional secretion and/or directional endocytic recycling. In plants, auxin efflux carrier PIN proteins display polar localizations in various cell types and play major roles in directional cell-to-cell transport of signaling molecule auxin that is vital for plant patterning and response programs. Recent advanced microscopy studies applied to single cells in intact plants reveal subcellular PIN dynamics. They uncover the PIN polarity generation mechanism and identified important roles of AGC kinases for polar PIN localization. AGC kinase family members PINOID, WAG1, and WAG2, belonging to the AGC-3 subclass predominantly influence the polar localization of PINs. The emerging mechanism for AGC-3 kinases action suggests that kinases phosphorylate PINs mainly at the plasma membrane after initial symmetric PIN secretion for eventual PIN internalization and PIN sorting into distinct ARF-GEF-regulated polar recycling pathways. Thus phosphorylation status directs PIN translocation to different cell sides. Based on these findings a mechanistic framework evolves that suggests existence of cell side-specific recycling pathways in plants and implicates AGC3 kinases for differential PIN recruitment among them for eventual PIN polarity establishment, maintenance, and alteration.

  16. Bioinspired Polarization Imaging Sensors: From Circuits and Optics to Signal Processing Algorithms and Biomedical Applications

    PubMed Central

    York, Timothy; Powell, Samuel B.; Gao, Shengkui; Kahan, Lindsey; Charanya, Tauseef; Saha, Debajit; Roberts, Nicholas W.; Cronin, Thomas W.; Marshall, Justin; Achilefu, Samuel; Lake, Spencer P.; Raman, Baranidharan; Gruev, Viktor

    2015-01-01

    In this paper, we present recent work on bioinspired polarization imaging sensors and their applications in biomedicine. In particular, we focus on three different aspects of these sensors. First, we describe the electro–optical challenges in realizing a bioinspired polarization imager, and in particular, we provide a detailed description of a recent low-power complementary metal–oxide–semiconductor (CMOS) polarization imager. Second, we focus on signal processing algorithms tailored for this new class of bioinspired polarization imaging sensors, such as calibration and interpolation. Third, the emergence of these sensors has enabled rapid progress in characterizing polarization signals and environmental parameters in nature, as well as several biomedical areas, such as label-free optical neural recording, dynamic tissue strength analysis, and early diagnosis of flat cancerous lesions in a murine colorectal tumor model. We highlight results obtained from these three areas and discuss future applications for these sensors. PMID:26538682

  17. Immature T-cell clustering and efficient differentiation require the polarity protein Scribble.

    PubMed

    Pike, Kelly A; Kulkarni, Sarang; Pawson, Tony

    2011-01-18

    T-cell polarization is required for cell migration and cell-cell interactions, cellular behaviors crucial for lymphocyte differentiation. Despite expression of the epithelial polarity network in T cells, neither its contribution to thymocyte polarity nor its requirement during development is known. We report here that depletion of the polarity protein Scribble in hematopoietic progenitor cells results in inefficient T-cell development characterized by a partial developmental block during the early double-negative (DN) stage of differentiation. Scribble-depleted hematopoietic progenitor cells exhibit a delayed transition into late CD44(lo/-)CD25(+) DN3 cells, evidenced by the accumulation of early CD44(int)CD25(+) DN3 cells. As a consequence, a limited cellular expansion and a reduced frequency of intracellular T-cell receptor β-positive DN3 cells are observed among Scribble-deficient differentiating T cells. Moreover, whereas purified Scribble-depleted DN2 and DN3 cells do not exhibit compromised spontaneous motility, T-cell clustering and prolonged homotypic interactions among such cells are reduced. This deficiency correlates with a lack of polarization of the integrin LFA-1 during T-cell migration or on the initiation of T-cell-T-cell interactions. Scribble is therefore a critical contributor to the clustering of immature T cells, an event shown here to be necessary for efficient developmental progression.

  18. Structural polarity and dynamics of male germline stem cells in the milkweed bug (Oncopeltus fasciatus).

    PubMed

    Schmidt, Esther D; Dorn, August

    2004-11-01

    The male germline stem cells (GSCs) of the milkweed bug present an extraordinary structural polarity that is, to our knowledge, unequalled by any other type of stem cells. They consist of a perikaryon and numerous projections arising from the cell pole directed toward the apical cells, the proposed niche of the GSCs. The projections can traverse a considerable distance until their terminals touch the apical cells. From hatching until death, the GSC projections undergo conspicuous changes, the sequence of which has been deduced from observations of all developmental stages. Projection formation starts from lobular cell protrusions showing trabecular ingrowths of the cell membrane. Finger-like projections result from a process of growth and "carving out". The newly formed projections contain mostly only free ribosomes other than a few mitochondria. A stereotyped degradation process commences in the projection terminals: profiles of circular, often concentric, cisternae of rough endoplasmic reticulum appear and turn into myelin bodies, whereas mitochondria become more numerous. The cytoplasm vesiculates, lysosomal bodies appear, and mitochondria become swollen. At the same time, the projection terminals are segregated by transverse ingrowths of the cell membrane. Finally, autophagic vacuoles and myelin bodies fill the segregated terminals, which then rupture. Simultaneously, new projections seem to sprout from the perikaryon of the GSCs. These dynamics, which are not synchronized among the GSCs, indicate that a novel type of signal exchange and transduction between the stem cells and their niche is involved in the regulation of asymmetric versus symmetric division of GSCs.

  19. Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism.

    PubMed

    Lowin-Kropf, B; Shapiro, V S; Weiss, A

    1998-02-23

    Binding of a T cell to an appropriate antigen-presenting cell (APC) induces the rapid reorientation of the T cell cytoskeleton and secretory apparatus towards the cell-cell contact site in a T cell antigen receptor (TCR) and peptide/major histocompatibility complex-dependent process. Such T cell polarization directs the delivery of cytokines and cytotoxic mediators towards the APC and contributes to the highly selective and specific action of effector T cells. To study the signaling pathways that regulate cytoskeletal rearrangements in T lymphocytes, we set up a conjugate formation assay using Jurkat T cells as effectors and cell-sized latex beads coated with various antibodies as artificial APCs. Here, we report that beads coated with antibodies specific for the TCR-CD3 complex were sufficient to induce T cell polarization towards the bead attachment site, as judged by reorientation of the microtubule-organizing center (MTOC) and localized actin polymerization. Thus, these cytoskeletal changes did not depend on activation of additional coreceptors. Moreover, single subunits of the TCR complex, namely TCR-zeta and CD3epsilon, were equally effective in inducing cytoskeletal polarization. However, mutagenesis of the immunoreceptor tyrosine-based activation motifs (ITAMs), present three times in TCR-zeta and once in CD3epsilon, revealed that the induction of cytoskeletal rearrangements required the presence of at least one intact ITAM. In agreement with this result, lack of functional Lck, the protein tyrosine kinase responsible for ITAM phosphorylation, abolished both MTOC reorientation and polarized actin polymerization. Both inhibitor and transient overexpression studies demonstrated that MTOC reorientation could occur in the absence of Ras activation. Our results suggest that APC-induced T cell polarization is a TCR-mediated event that is coupled to the TCR by the same signaling motif as TCR-induced gene activation, but diverges in its distal signaling

  20. The variable polarity plasma arc welding process: Its application to the Space Shuttle external tank

    NASA Technical Reports Server (NTRS)

    Nunes, A. C., Jr.; Bayless, O. E., Jr.; Jones, C. S., III; Munafo, A. P.; Wilson, W. A.

    1983-01-01

    The technical history of the variable polarity plasma arc (VPPA) welding process being introduced as a partial replacement for the gas shielded tungsten arc process in assembly welding of the space shuttle external tank is described. Interim results of the weld strength qualification studies, and plans for further work on the implementation of the VPPA process are included.

  1. Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

    PubMed

    Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

    2016-04-01

    Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The Hedgehog pathway: role in cell differentiation, polarity and proliferation.

    PubMed

    Jia, Yanfei; Wang, Yunshan; Xie, Jingwu

    2015-02-01

    Hedgehog (Hh) is first described as a genetic mutation that has "spiked" phenotype in the cuticles of Drosophila in later 1970s. Since then, Hh signaling has been implicated in regulation of differentiation, proliferation, tissue polarity, stem cell population and carcinogenesis. The first link of Hh signaling to cancer was established through discovery of genetic mutations of Hh receptor gene PTCH1 being responsible for Gorlin syndrome in 1996. It was later shown that Hh signaling is associated with many types of cancer, including skin, leukemia, lung, brain and gastrointestinal cancers. Another important milestone for the Hh research field is the FDA approval for the clinical use of Hh inhibitor Erivedge/Vismodegib for treatment of locally advanced and metastatic basal cell carcinomas. However, recent clinical trials of Hh signaling inhibitors in pancreatic, colon and ovarian cancer all failed, indicating a real need for further understanding of Hh signaling in cancer. In this review, we will summarize recent progress in the Hh signaling mechanism and its role in human cancer.

  3. Polarized expression of Shaker channels in epithelial cells.

    PubMed

    Moreno, J; Cruz-Vera, L R; García-Villegas, M R; Cereijido, M

    2002-12-01

    The polarized distribution of ion channels into an apical or a basolateral domain is a fundamental feature of the transporting-epithelial phenotype. To study the molecular motifs of the channel that may serve as addressing signal(s), as well as the cellular mechanisms that interpret it and deliver the protein accordingly, we study the fate of transfected ShIR K+ channels (a non-inactivating Shaker channel) tagged with an HA epitope, as well as several other deletants and mutants. Surface expression is triggered by Ca2+-activated cell-cell contacts, through a cascade including a phospholipase C, a protein kinase C, and the cytoskeleton of actin and tubulin, and is partially impaired by suppressing N-glycosylation with tunicamycin. Using domain-specific biotinylation we show that the channel is delivered preferentially to the basolateral domain thanks to a segment between amino acids 571 and 613, and is retained on the membrane surface due to a region involving the last three amino acids (threonine, aspartic acid, valine, TDV) of the COOH terminal. Its association with the cytoskeleton seems to take the form of a scaffold comprising actin, a-actinin, b-tubulin, mLin7 and CASK. We also observe that membrane expression of ShIR channels depends entirely on its sequence of amino acids and the conformation that the molecule may adopt, but not on its ability to translocate K+ across the membrane.

  4. Tissue-wide Mechanical Forces Influence the Polarity of Stomatal Stem Cells in Arabidopsis.

    PubMed

    Bringmann, Martin; Bergmann, Dominique C

    2017-03-20

    Mechanical information is an important contributor to cell polarity in uni- and multicellular systems [1-3]. In planar tissues like the Drosophila wing, cell polarity reorients during growth as cells divide and reorganize [4]. In another planar tissue, the Arabidopsis leaf epidermis [5], polarized, asymmetric divisions of stomatal stem cells (meristemoid mother cells [MMCs]) are fundamental for the generation and patterning of multiple cell types, including stomata. The activity of key transcription factors, polarizing factors [6], and peptide signals [7] explains some local stomatal patterns emerging from the behavior of a few lineally related cells [6, 8-11]. Here we demonstrate that, in addition to locally acting signals, tissue-wide mechanical forces can act as organizing cues, and that they do so by influencing the polarity of individual MMCs. If the mechanical stress environment in the tissue is altered through stretching or cell ablations, cellular polarity changes in response. In turn, polarity predicts the orientation of cellular and tissue outgrowth, leading to increased mechanical conflicts between neighboring cells. This interplay among growth, oriented divisions, and cell specification could contribute to the characteristic patterning of stomatal guard cells in the context of a growing leaf.

  5. Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration.

    PubMed

    Rodrigo Albors, Aida; Tazaki, Akira; Rost, Fabian; Nowoshilow, Sergej; Chara, Osvaldo; Tanaka, Elly M

    2015-11-14

    Axolotls are uniquely able to mobilize neural stem cells to regenerate all missing regions of the spinal cord. How a neural stem cell under homeostasis converts after injury to a highly regenerative cell remains unknown. Here, we show that during regeneration, axolotl neural stem cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial cells. This dedifferentiation includes the acquisition of rapid cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative stem cell that restores missing tissue.

  6. Proceedings of a Workshop on Polar Stratospheric Clouds: Their Role in Atmospheric Processes

    NASA Technical Reports Server (NTRS)

    Hamill, P. (Editor); Mcmaster, L. R. (Editor)

    1984-01-01

    The potential role of polar stratospheric clouds in atmospheric processes was assessed. The observations of polar stratospheric clouds with the Nimbus 7 SAM II satellite experiment were reviewed and a preliminary analysis of their formation, impact on other remote sensing experiments, and potential impact on climate were presented. The potential effect of polar stratospheric clouds on climate, radiation balance, atmospheric dynamics, stratospheric chemistry and water vapor budget, and cloud microphysics was assessed. Conclusions and recommendations, a synopsis of materials and complementary material to support those conclusions and recommendations are presented.

  7. Features of the processes of ion heating in polar boundary of the night auroral oval

    NASA Astrophysics Data System (ADS)

    Chugunin, Dmitriy; Lutsenko, Volt; Romantsova, Tatiana; Mogilevsky, Mikhail; Moiseenko, Irina

    Investigation of the processes of ion heating in polar boundary of the night auroral oval measured by INTERBALL-2 (Auroral probe) is presented. Measurements of particles and waves were made on altitude about 20000 км. Feature of the orbits was the satellite slid along auroral oval and stay long time in the auroral zone. It were cases chosen when the polar boundary moved and passed through satellite. Particular attention is given to ions heating at this border and to ion heating position in relation to polar boundary of particle precipitation.

  8. A Polarized Cell Model for Chikungunya Virus Infection: Entry and Egress of Virus Occurs at the Apical Domain of Polarized Cells

    PubMed Central

    Lim, Pei Jin; Chu, Justin Jang Hann

    2014-01-01

    Chikungunya virus (CHIKV) has resulted in several outbreaks in the past six decades. The clinical symptoms of Chikungunya infection include fever, skin rash, arthralgia, and an increasing incidence of encephalitis. The re-emergence of CHIKV with more severe pathogenesis highlights its potential threat on our human health. In this study, polarized HBMEC, polarized Vero C1008 and non-polarized Vero cells grown on cell culture inserts were infected with CHIKV apically or basolaterally. Plaque assays, viral binding assays and immunofluorescence assays demonstrated apical entry and release of CHIKV in polarized HBMEC and Vero C1008. Drug treatment studies were performed to elucidate both host cell and viral factors involved in the sorting and release of CHIKV at the apical domain of polarized cells. Disruption of host cell myosin II, microtubule and microfilament networks did not disrupt the polarized release of CHIKV. However, treatment with tunicamycin resulted in a bi-directional release of CHIKV, suggesting that N-glycans of CHIKV envelope glycoproteins could serve as apical sorting signals. PMID:24587455

  9. Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development

    PubMed Central

    Tikhmyanova, Nadezhda; Tulin, Alexei V.; Roegiers, Fabrice; Golemis, Erica A.

    2010-01-01

    Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and β-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development. PMID:20808771

  10. Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity.

    PubMed

    Hawkins, Edwin D; Oliaro, Jane; Kallies, Axel; Belz, Gabrielle T; Filby, Andrew; Hogan, Thea; Haynes, Nicole; Ramsbottom, Kelly M; Van Ham, Vanessa; Kinwell, Tanja; Seddon, Benedict; Davies, Derek; Tarlinton, David; Lew, Andrew M; Humbert, Patrick O; Russell, Sarah M

    2013-01-01

    The production of protective antibody requires effective signalling of naive B cells following encounter with antigen, and the divergence of responding B lymphocytes into distinct lineages. Polarity proteins have recently been proposed as important mediators of both the initial B cell response, and potentially of asymmetric cell division. Here we show that, although polarity proteins of the Scribble complex, Scribble, Dlg1 and Lgl1, are expressed and polarized during early B cell activation, their deficiency has no effect on the in vivo outcome of immunization or challenge with influenza infection. Furthermore, we find a striking correlation in the differentiation outcome of daughters of single founder B cells in vitro. Taken together, our results indicate that B cell differentiation does not require polarity proteins of the Scribble complex, and the findings do not support a role for asymmetric cell division in B cell activation and differentiation.

  11. Beyond polarity: functional membrane domains in astrocytes and Müller cells.

    PubMed

    Derouiche, Amin; Pannicke, Thomas; Haseleu, Julia; Blaess, Sandra; Grosche, Jens; Reichenbach, Andreas

    2012-11-01

    Various ependymoglial cells display varying degrees of process specialization, in particular processes contacting mesenchymal borders (pia, blood vessels, vitreous body), or those lining the ventricular surface. Within the neuropil, glial morphology, cellular contacts, and interaction partners are complex. It appears that glial processes contacting neurons, specific parts of neurons, or mesenchymal or ventricular borders are characterized by specialized membranes. We propose a concept of membrane domains in addition to the existing concept of ependymoglial polarity. Such membrane domains are equipped with certain membrane-bound proteins, enabling them to function in their specific environment. This review focuses on Müller cells and astrocytes and discusses exemplary the localization of established glial markers in membrane domains. We distinguish three functional glial membrane domains based on their typical molecular arrangement. The domain of the endfoot specifically displays the complex of dystrophin-associated proteins, aquaporin 4 and the potassium channel Kir4.1. We show that the domain of microvilli and the peripheral glial process in the Müller cell share the presence of ezrin, as do peripheral astrocyte processes. As a third domain, the Müller cell has peripheral glial processes related to a specific subtype of synapse. Although many details remain to be studied, the idea of glial membrane domains may permit new insights into glial function and pathology.

  12. CIDEP study of two photochemical processes of triplet-state benzophenone and N,N-diethylaniline system in polar and non-polar media

    NASA Astrophysics Data System (ADS)

    Miyagawa, K.; Murai, H.; I'Haya, Y. J.

    1985-07-01

    The photochemical reactions between nπ * triplet benzophenone and N,N-diethylaniline have been studied by the CIDEP method in both polar and non-polar media. The total emission pattern of the spectrum detected after pulsed excitation reveals a predominant contribution of the triplet mechanism in both media. The observed CIDEP clearly indicates the existence of two different processes depending on the polarity of the solvents.

  13. Salmonella enterica Invasion of Polarized Epithelial Cells Is a Highly Cooperative Effort

    PubMed Central

    Lorkowski, Martin; Felipe-López, Alfonso; Danzer, Claudia A.; Hansmeier, Nicole

    2014-01-01

    The invasion of polarized epithelial cells by Salmonella enterica requires the cooperative activity of the Salmonella pathogenicity island 1 (SPI1)-encoded type III secretion system (T3SS) and the SPI4-encoded adhesin SiiE. The invasion of polarized cells is more efficient than that of nonpolarized cells, and we observed the formation of clusters of bacteria on infected cells. Here we demonstrate that the invasion of polarized cells is a highly cooperative activity. Using a novel live-cell imaging approach, we visualized the cooperative entry of multiple bacteria into ruffles induced on the apical surfaces of polarized cells. The induction of membrane ruffles by activity of Salmonella enables otherwise noninvasive mutant strains to enter polarized host cells. Bacterial motility and chemotaxis were of lower importance for cooperativity in polarized-cell invasion. We propose that cooperative invasion is a key factor for the very efficient entry into polarized cells and a factor contributing to epithelial damage and intestinal inflammation. PMID:24711567

  14. AKT-mediated regulation of polarization in differentiated human neutrophil-like HL-60 cells.

    PubMed

    Zou, Wenying; Chu, Xinwei; Cai, Chunqing; Zou, Mengchen; Meng, Xiaojing; Chen, Haiyang; Zou, Fei

    2012-08-01

    Neutrophil polarization is critical for the inflammatory response. AKT is a serine/threonine protein kinase and has been implicated in cell migration. However, it is not completely clear whether AKT affects neutrophil polarization. In this study, we tested the hypothesis that AKT regulates the polarization of neutrophil-like differentiated HL-60 cells (dHL-60) in response to fMLP. HL-60 cells were differentiated into dHL-60 by incubation in medium containing 1.3 % DMSO for up to 6 days. Polarization of dHL-60 cells and primary human neutrophils were measured by Zigmond chamber. Phospho-Akt was analyzed by immunofluorescence and Western blot analysis. F-actin polymerization was detected by Rhodamine-Phalloidine staining. Rac2 activation was evaluated using GST Pull-down assay. We found that changes in the rate of cell polarization were consistent with the changes in AKT phosphorylation levels during HL-60 cell differentiation in response to fMLP. Moreover, cell polarization and AKT phosphorylation were reduced in fMLP-stimulated dHL-60 cells pretreated with the PI3 kinase inhibitors or the AKT inhibitors, which was confirmed in the primary human neutrophils. The AKT inhibitors altered fMLP-induced F-actin polymerization. Rac2 GTPases was also decreased by the AKT inhibitors in fMLP-stimulated dHL-60 cells. This study demonstrates that AKT activation plays a crucial role in dHL-60 cell polarization.

  15. Central Roles of Small GTPases in the Development of Cell Polarity in Yeast and Beyond

    PubMed Central

    Park, Hay-Oak; Bi, Erfei

    2007-01-01

    Summary: The establishment of cell polarity is critical for the development of many organisms and for the function of many cell types. A large number of studies of diverse organisms from yeast to humans indicate that the conserved, small-molecular-weight GTPases function as key signaling proteins involved in cell polarization. The budding yeast Saccharomyces cerevisiae is a particularly attractive model because it displays pronounced cell polarity in response to intracellular and extracellular cues. Cells of S. cerevisiae undergo polarized growth during various phases of their life cycle, such as during vegetative growth, mating between haploid cells of opposite mating types, and filamentous growth upon deprivation of nutrition such as nitrogen. Substantial progress has been made in deciphering the molecular basis of cell polarity in budding yeast. In particular, it becomes increasingly clear how small GTPases regulate polarized cytoskeletal organization, cell wall assembly, and exocytosis at the molecular level and how these GTPases are regulated. In this review, we discuss the key signaling pathways that regulate cell polarization during the mitotic cell cycle and during mating. PMID:17347519

  16. Polar lacuna on ionograms. E- or F-region processes?

    NASA Astrophysics Data System (ADS)

    Stauning, P.

    1995-04-01

    Lacuna on ionograms indicate conditions where the usual ionospheric reflections of vertically propagating radio waves transmitted from and subsequently received by an ionosonde are missing over a range of frequencies. Reflections from the lowermost E-region should still be observable contrary to the more usual cases where absorption processes in the underlying D-region removes the low-frequency part of the ionospheric reflections appearing in ionograms. It is emphasized below that lacuna cases related to E-region processes should be distinguished from lacunae related to processes in the F1 and F2 regions. This distinction appears to have been neglected in a recent paper.

  17. Cloning and expression of Xenopus Prickle, an orthologue of a Drosophila planar cell polarity gene.

    PubMed

    Wallingford, John B; Goto, Toshiyasu; Keller, Ray; Harland, Richard M

    2002-08-01

    We have cloned Xenopus orthologues of the Drosophila planar cell polarity (PCP) gene Prickle. Xenopus Prickle (XPk) is expressed in tissues at the dorsal midline during gastrulation and early neurulation. XPk is later expressed in a segmental pattern in the presomitic mesoderm and then in recently formed somites. XPk is also expressed in the tailbud, pronephric duct, retina, and the otic vesicle. The complex expression pattern of XPk suggests that PCP signaling is used in a diverse array of developmental processes in vertebrate embryos.

  18. Polarization Processes of Nanocomposite Silicate-EVA and PP Materials

    NASA Astrophysics Data System (ADS)

    Montanari, Gian Carlo; Palmieri, Fabrizio; Testa, Luigi; Motori, Antonio; Saccani, Andrea; Patuelli, Francesca

    Recent works indicate that polypropylene (PP) and ethylene-vinylacetate (EVA) filled by nanosilicates may present low content of space charge and high electric strength. Investigations are being made to explain nanocomposite behaviour and characterize their electrical, thermal and mechanical properties. In this paper, the results of broad-band dielectric spectroscopy performed on EVA and PP filled by layered nanosized silicates are reported. Isochronal and isothermal curves of complex permittivity, as well as activation energies of the relaxation processes, are presented and discussed. Nanostructuration gives rise to substantial changes in the polarisation and dielectric loss behaviour. While the relaxation process of EVA, associated with glass transition of the material amorphous phase, results unchanged from base to nanostructured material, nanocomposites EVA and PP have shown the rise of a new process at higher temperatures respect to the typical host material processes, as well as a different distribution of relaxation processes. Changes in space charge accumulation in relation to the effectiveness of the purification process performed upon nanostructured materials are also reported: while the dispersion of the clean clays leads to a reduction of the space charge, especially at high fields, an unclean filler gives rise to significant homo-charge accumulation and interfacial polarisation phenomena.

  19. Neurotypic cell attachment and growth on III-nitride lateral polarity structures.

    PubMed

    Bain, L E; Kirste, R; Johnson, C A; Ghashghaei, H T; Collazo, R; Ivanisevic, A

    2016-01-01

    III-nitride materials have recently received increasing levels of attention for their potential to successfully interface with, and sense biochemical interactions in biological systems. Expanding on available sensing schemes (including transistor-based devices,) a III-N lateral polarity structure capable of introducing quasi-phase matching through a periodic polarity grating presents a novel platform for second harmonic generation. This platform constitutes a non-linear optical phenomenon with exquisite sensitivity to the chemical state of a surface or interface. To characterize the response of a biological system to the nanostructured lateral polarity structures, we cultured neurotypic PC12 cells on AlGaN with varying ratios of Al:Ga - 0, 0.4, 0.6, and 1 - and on surfaces of varying pitch to the III-polar vs. N-polar grating - 5, 10, 20 and 50 μm. While some toxicity associated with increasing Al is observed, we documented and quantified trends in cell responses to the local material polarity and nanoscale roughness. The nitrogen-polar material has a significantly higher nanoscale roughness than III-polar regions, and a 80-200 nm step height difference between the III-polar and N-polar materials in the lateral polarity configuration generates adequate changes in topography to influence cell growth, improves cell adhesion and promotes cell migration along the direction of the features. As the designed material configuration is further explored for biochemical sensing, the lateral polarity scheme may provide a route in assessing the non-specific protein adsorption to this varying nano-topography that drives the subsequent cell response.

  20. Role of the Polycystins in Cell Migration, Polarity, and Tissue Morphogenesis

    PubMed Central

    Nigro, Elisa Agnese; Castelli, Maddalena; Boletta, Alessandra

    2015-01-01

    Cystic kidney diseases (CKD) is a class of disorders characterized by ciliary dysfunction and, therefore, belonging to the ciliopathies. The prototype CKD is autosomal dominant polycystic kidney disease (ADPKD), whose mutated genes encode for two membrane-bound proteins, polycystin-1 (PC-1) and polycystin-2 (PC-2), of unknown function. Recent studies on CKD-associated genes identified new mechanisms of morphogenesis that are central for establishment and maintenance of proper renal tubular diameter. During embryonic development in the mouse and lower vertebrates a convergent-extension (CE)-like mechanism based on planar cell polarity (PCP) and cellular intercalation is involved in “sculpting” the tubules into a narrow and elongated shape. Once the appropriate diameter is established, further elongation occurs through oriented cell division (OCD). The polycystins (PCs) regulate some of these essential processes. In this review we summarize recent work on the role of PCs in regulating cell migration, the cytoskeleton, and front-rear polarity. These important properties are essential for proper morphogenesis of the renal tubules and the lymphatic vessels. We highlight here several open questions and controversies. Finally, we try to outline some of the next steps required to study these processes and their relevance in physiological and pathological conditions. PMID:26529018

  1. The polarity protein Baz forms a platform for the centrosome orientation during asymmetric stem cell division in the Drosophila male germline.

    PubMed

    Inaba, Mayu; Venkei, Zsolt G; Yamashita, Yukiko M

    2015-03-20

    Many stem cells divide asymmetrically in order to balance self-renewal with differentiation. The essence of asymmetric cell division (ACD) is the polarization of cells and subsequent division, leading to unequal compartmentalization of cellular/extracellular components that confer distinct cell fates to daughter cells. Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood. In Drosophila male germline stem cells, ACD is prepared by stereotypical centrosome positioning. The centrosome orientation checkpoint (COC) further serves to ensure ACD by preventing mitosis upon centrosome misorientation. In this study, we show that Bazooka (Baz) provides a platform for the correct centrosome orientation and that Baz-centrosome association is the key event that is monitored by the COC. Our work provides a foundation for understanding how the correct cell polarity may be recognized by the cell to ensure productive ACD.

  2. ROP GTPases act with the receptor-like protein PAN1 to polarize asymmetric cell division in maize.

    PubMed

    Humphries, John A; Vejlupkova, Zuzana; Luo, Anding; Meeley, Robert B; Sylvester, Anne W; Fowler, John E; Smith, Laurie G

    2011-06-01

    Plant Rho family GTPases (ROPs) have been investigated primarily for their functions in polarized cell growth. We previously showed that the maize (Zea mays) Leu-rich repeat receptor-like protein PANGLOSS1 (PAN1) promotes the polarization of asymmetric subsidiary mother cell (SMC) divisions during stomatal development. Here, we show that maize Type I ROPs 2 and 9 function together with PAN1 in this process. Partial loss of ROP2/9 function causes a weak SMC division polarity phenotype and strongly enhances this phenotype in pan1 mutants. Like PAN1, ROPs accumulate in an asymmetric manner in SMCs. Overexpression of yellow fluorescent protein-ROP2 is associated with its delocalization in SMCs and with aberrantly oriented SMC divisions. Polarized localization of ROPs depends on PAN1, but PAN1 localization is insensitive to depletion and depolarization of ROP. Membrane-associated Type I ROPs display increased nonionic detergent solubility in pan1 mutants, suggesting a role for PAN1 in membrane partitioning of ROPs. Finally, endogenous PAN1 and ROP proteins are physically associated with each other in maize tissue extracts, as demonstrated by reciprocal coimmunoprecipitation experiments. This study demonstrates that ROPs play a key role in polarization of plant cell division and cell growth and reveals a role for a receptor-like protein in spatial localization of ROPs.

  3. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure

    PubMed Central

    McGreevy, Erica M.; Vijayraghavan, Deepthi; Davidson, Lance A.; Hildebrand, Jeffrey D.

    2015-01-01

    ABSTRACT Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP) pathway, to direct the polarized cellular behaviors that drive convergent extension (CE) movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs. PMID:25596276

  4. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure.

    PubMed

    McGreevy, Erica M; Vijayraghavan, Deepthi; Davidson, Lance A; Hildebrand, Jeffrey D

    2015-01-16

    Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP) pathway, to direct the polarized cellular behaviors that drive convergent extension (CE) movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs. © 2015. Published by The Company of Biologists Ltd.

  5. Measurement of relative phase distribution of onion epidermal cells by using the polarization microscope

    NASA Astrophysics Data System (ADS)

    Shin, In Hee; Lee, Ji Yong; Lee, Seungrag; Lee, Dong Ju; Kim, Dug Young

    2007-02-01

    Bio-cells and tissues have intrinsic polarization characteristics, which are changed by external stimulus and internal metamorphosis in cells and tissues and some of the bio-cells and tissues have intrinsic birefringence characteristics, which are also changed by external stimulus and internal metamorphosis in cells and tissues. In this paper, we have developed the polarization microscope for measurement of relative phase which results from birefringence characteristics of materials with improved linear polarizing method and have measured relative phase distribution of onion epidermal cells. From the measurement of the relative phase distribution of onion epidermal cells, decrease of relative phase distribution of onion epidermal cells was investigated as the elapse of time. In decrease of relative phase distribution, relative phase of cell membrane in onion epidermal cells decreased radically as compared with that of cytoplasm because decline of function in cell membrane that takes charge of matter transfer in onion epidermal cells has occurred.

  6. 10.6% Certified Colloidal Quantum Dot Solar Cells via Solvent-Polarity-Engineered Halide Passivation.

    PubMed

    Lan, Xinzheng; Voznyy, Oleksandr; García de Arquer, F Pelayo; Liu, Mengxia; Xu, Jixian; Proppe, Andrew H; Walters, Grant; Fan, Fengjia; Tan, Hairen; Liu, Min; Yang, Zhenyu; Hoogland, Sjoerd; Sargent, Edward H

    2016-07-13

    Colloidal quantum dot (CQD) solar cells are solution-processed photovoltaics with broad spectral absorption tunability. Major advances in their efficiency have been made via improved CQD surface passivation and device architectures with enhanced charge carrier collection. Herein, we demonstrate a new strategy to improve further the passivation of CQDs starting from the solution phase. A cosolvent system is employed to tune the solvent polarity in order to achieve the solvation of methylammonium iodide (MAI) and the dispersion of hydrophobic PbS CQDs simultaneously in a homogeneous phase, otherwise not achieved in a single solvent. This process enables MAI to access the CQDs to confer improved passivation. This, in turn, allows for efficient charge extraction from a thicker photoactive layer device, leading to a certified solar cell power conversion efficiency of 10.6%, a new certified record in CQD photovoltaics.

  7. Processing Polarity: How the Ungrammatical Intrudes on the Grammatical

    ERIC Educational Resources Information Center

    Vasishth, Shravan; Brussow, Sven; Lewis, Richard L.; Drenhaus, Heiner

    2008-01-01

    A central question in online human sentence comprehension is, "How are linguistic relations established between different parts of a sentence?" Previous work has shown that this dependency resolution process can be computationally expensive, but the underlying reasons for this are still unclear. This article argues that dependency…

  8. Processing Polarity: How the Ungrammatical Intrudes on the Grammatical

    ERIC Educational Resources Information Center

    Vasishth, Shravan; Brussow, Sven; Lewis, Richard L.; Drenhaus, Heiner

    2008-01-01

    A central question in online human sentence comprehension is, "How are linguistic relations established between different parts of a sentence?" Previous work has shown that this dependency resolution process can be computationally expensive, but the underlying reasons for this are still unclear. This article argues that dependency…

  9. Wnt and planar cell polarity signaling in cystic renal disease.

    PubMed

    Goggolidou, Paraskevi

    2014-01-01

    Cystic kidney diseases can cause end stage renal disease, affecting millions of individuals worldwide. They may arise early or later in life, are characterized by a spectrum of symptoms and can be caused by diverse genetic defects. The primary cilium, a microtubule-based organelle that can serve as a signaling antenna, has been demonstrated to have a significant role in ensuring correct kidney development and function. In the kidney, one of the signaling pathways that requires the cilium for normal development is Wnt signaling. In this review, the roles of primary cilia in relation to canonical and non-canonical Wnt/PCP signaling in cystic renal disease are described. The evidence of the associations between cilia, Wnt signaling and cystic renal disease is discussed and the significance of planar cell polarity-related mechanisms in cystic kidney disease is presented. Although defective Wnt signaling is not the only cause of renal disease, research is increasingly highlighting its importance, encouraging the development of Wnt-associated diagnostic and prognostic tools for cystic renal disease.

  10. A self-propelled particle model with experimentally quantified cell polarization

    NASA Astrophysics Data System (ADS)

    Passucci, Giuseppe; Brasch, Megan E.; Deakin, Nicholas O.; Turner, Christopher E.; Henderson, James H.; Manning, M. Lisa

    2015-03-01

    Self-propelled particle (SPP) models have been used extensively to study collective cell motion, but they do not always accurately capture the long-time behavior observed in experiments. Furthermore, the equation for polarization in these models is not experimentally well-constrained. Therefore we developed a novel method for quantifying polarization in Hs578T breast carcinoma cells in a wound healing geometry. During cell movement, the nucleus orients toward the anterior of a cell while the Golgi body orients towards the posterior; we simultaneously imaged and tracked the Golgi and nuclei and constructed a polarization vector defined by the Golgi-nuclei axis. We find that cells in the bulk are not highly polarized, while those on the edge are highly polarized outward perpendicular to the wound edge. We also study the temporal correlations between a cell's internal polarization determined by the Golgi-nuclei axis and the polarization of its motion determined from nuclei displacements. We incorporate these polarization dynamics into a SPP model, and compare wound healing and long-time diffusion in the model to the experiments. These SPP equations can also be coarse-grained to generate a continuum model.

  11. Flotillins are involved in the polarization of primitive and mature hematopoietic cells.

    PubMed

    Rajendran, Lawrence; Beckmann, Julia; Magenau, Astrid; Boneberg, Eva-Maria; Gaus, Katharina; Viola, Antonella; Giebel, Bernd; Illges, Harald

    2009-12-22

    Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues. Here, we present evidence that raft-associated endocytic proteins (flotillins) are pre-assembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions. Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization.

  12. Influence of polar solvents on photovoltaic performance of Monascusred dye-sensitized solar cell.

    PubMed

    Lee, Jae Wook; Kim, Tae Young; Ko, Hyun Seok; Han, Shin; Lee, Suk-Ho; Park, Kyung Hee

    2014-05-21

    Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from Monascus red pigment as a sensitizer. In this work, we studied the adsorption characteristics for harvesting sunlight and the electrochemical behavior for electron transfer in Monascus red DSSC using different solvents. The effect of polar aprotic and protic solvents including water, ethanol, and dimethylsulfoxide (DMSO) used in the sensitization process was investigated for the improvement in conversion efficiency of a cell. As for the Monascus red dye-sensitized electrode in DMSO solvent, the solar cell yields a short-circuit current density (Jsc) of 1.23mA/cm(2), a photovoltage (Voc) of 0.75V, and a fill factor of 0.72, corresponding to an energy conversion efficiency (η) of 0.66%.

  13. Influence of polar solvents on photovoltaic performance of Monascusred dye-sensitized solar cell

    NASA Astrophysics Data System (ADS)

    Lee, Jae Wook; Kim, Tae Young; Ko, Hyun Seok; Han, Shin; Lee, Suk-Ho; Park, Kyung Hee

    Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from Monascus red pigment as a sensitizer. In this work, we studied the adsorption characteristics for harvesting sunlight and the electrochemical behavior for electron transfer in Monascus red DSSC using different solvents. The effect of polar aprotic and protic solvents including water, ethanol, and dimethylsulfoxide (DMSO) used in the sensitization process was investigated for the improvement in conversion efficiency of a cell. As for the Monascus red dye-sensitized electrode in DMSO solvent, the solar cell yields a short-circuit current density (Jsc) of 1.23 mA/cm2, a photovoltage (Voc) of 0.75 V, and a fill factor of 0.72, corresponding to an energy conversion efficiency (η) of 0.66%.

  14. Subnanosecond polarized microfluorimetry in the time domain: An instrument for studying receptor trafficking in live cells

    NASA Astrophysics Data System (ADS)

    Martin-Fernandez, M. L.; Tobin, M. J.; Clarke, D. T.; Gregory, C. M.; Jones, G. R.

    1998-02-01

    We describe an instrument designed to monitor molecular motions in multiphasic, weakly fluorescent microscopic systems. It combines synchrotron radiation, a low irradiance polarized microfluorimeter, and an automated, multiframing, single-photon-counting data acquisition system, and is capable of continually accumulating subnanosecond resolved anisotropy decays with a real-time resolution of about 60 s. The instrument has initially been built to monitor ligand-receptor interactions in living cells, but can equally be applied to the continual measurement of any dynamic process involving fluorescent molecules, that occurs over a time scale from a few minutes to several hours. As a particularly demanding demonstration of its capabilities, we have used it to monitor the environmental constraints imposed on the peptide hormone epidermal growth factor during its endocytosis and recycling to the cell surface in live cells.

  15. Solar cell module lamination process

    DOEpatents

    Carey, Paul G.; Thompson, Jesse B.; Aceves, Randy C.

    2002-01-01

    A solar cell module lamination process using fluoropolymers to provide protection from adverse environmental conditions and thus enable more extended use of solar cells, particularly in space applications. A laminate of fluoropolymer material provides a hermetically sealed solar cell module structure that is flexible and very durable. The laminate is virtually chemically inert, highly transmissive in the visible spectrum, dimensionally stable at temperatures up to about 200.degree. C. highly abrasion resistant, and exhibits very little ultra-violet degradation.

  16. The BASL Polarity Protein Controls a MAPK Signaling Feedback Loop in Asymmetric Cell Division

    PubMed Central

    Zhang, Ying; Wang, Pengcheng; Shao, Wanchen; Zhu, Jian-Kang; Dong, Juan

    2015-01-01

    SUMMARY Cell polarization is linked to fate determination during asymmetric division of plant stem cells, but the underlying molecular mechanisms remain unknown. In Arabidopsis, BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) is polarized to control stomatal asymmetric division. A MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) cascade determines terminal stomatal fate by promoting the degradation of the lineage determinant SPEECHLESS (SPCH). Here we demonstrate that a positive feedback loop between BASL and the MAPK pathway constitutes a polarity module at the cortex. Cortical localization of BASL requires phosphorylation mediated by MPK3/6. Phosphorylated BASL functions as a scaffold and recruits the MAPKKK YODA and MPK3/6 to spatially concentrate signaling at the cortex. Activated MPK3/6 reinforces the feedback loop by phosphorylating BASL, and inhibits stomatal fate by phosphorylating SPCH. Polarization of the BASL-MAPK signaling feedback module represents a mechanism connecting cell polarity to fate differentiation during asymmetric stem cell division in plants. PMID:25843888

  17. PrPC Undergoes Basal to Apical Transcytosis in Polarized Epithelial MDCK Cells

    PubMed Central

    Arkhipenko, Alexander; Syan, Sylvie; Victoria, Guiliana Soraya

    2016-01-01

    The Prion Protein (PrP) is an ubiquitously expressed glycosylated membrane protein attached to the external leaflet of the plasma membrane via a glycosylphosphatidylinositol anchor (GPI). While the misfolded PrPSc scrapie isoform is the infectious agent of prion disease, the cellular isoform (PrPC) is an enigmatic protein with unclear function. Of interest, PrP localization in polarized MDCK cells is controversial and its mechanism of trafficking is not clear. Here we investigated PrP traffic in MDCK cells polarized on filters and in three-dimensional MDCK cysts, a more physiological model of polarized epithelia. We found that, unlike other GPI-anchored proteins (GPI-APs), PrP undergoes basolateral-to-apical transcytosis in fully polarized MDCK cells. Following this event full-length PrP and its cleavage fragments are segregated in different domains of the plasma membrane in polarized cells in both 2D and 3D cultures. PMID:27389581

  18. Role of host cell polarity and leading edge properties in Pseudomonas type III secretion

    PubMed Central

    Bridge, Dacie R.; Novotny, Matthew J.; Moore, Elizabeth R.; Olson, Joan C.

    2010-01-01

    Type III secretion (T3S) functions in establishing infections in a large number of Gram-negative bacteria, yet little is known about how host cell properties might function in this process. We used the opportunistic pathogen Pseudomonas aeruginosa and the ability to alter host cell sensitivity to Pseudomonas T3S to explore this problem. HT-29 epithelial cells were used to study cellular changes associated with loss of T3S sensitivity, which could be induced by treatment with methyl-beta-cyclodextrin or perfringolysin O. HL-60 promyelocytic cells are innately resistant to Pseudomonas T3S and were used to study cellular changes occurring in response to induction of T3S sensitivity, which occurred following treatment with phorbol esters. Using both cell models, a positive correlation was observed between eukaryotic cell adherence to tissue culture wells and T3S sensitivity. In examining the type of adhesion process linked to T3S sensitivity in HT-29 cells, a hierarchical order of protein involvement was identified that paralleled the architecture of leading edge (LE) focal complexes. Conversely, in HL-60 cells, induction of T3S sensitivity coincided with the onset of LE properties and the development of actin-rich projections associated with polarized cell migration. When LE architecture was examined by immunofluorescent staining for actin, Rac1, IQ-motif-containing GTPase-activating protein 1 (IQGAP1) and phosphatidylinositol 3 kinase (PI3 kinase), intact LE structure was found to closely correlate with host cell sensitivity to P. aeruginosa T3S. Our model for host cell involvement in Pseudomonas T3S proposes that cortical actin polymerization at the LE alters membrane properties to favour T3S translocon function and the establishment of infections, which is consistent with Pseudomonas infections targeting wounded epithelial barriers undergoing cell migration. PMID:19910414

  19. Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II.

    PubMed

    Hirota, Yuki; Meunier, Alice; Huang, Shihhui; Shimozawa, Togo; Yamada, Osamu; Kida, Yasuyuki S; Inoue, Masashi; Ito, Tsubasa; Kato, Hiroko; Sakaguchi, Masanori; Sunabori, Takehiko; Nakaya, Masa-Aki; Nonaka, Shigenori; Ogura, Toshihiko; Higuchi, Hideo; Okano, Hideyuki; Spassky, Nathalie; Sawamoto, Kazunobu

    2010-09-01

    Motile cilia generate constant fluid flow over epithelial tissue, and thereby influence diverse physiological processes. Such functions of ciliated cells depend on the planar polarity of the cilia and on their basal bodies being oriented in the downstream direction of fluid flow. Recently, another type of basal body planar polarity, characterized by the anterior localization of the basal bodies in individual cells, was reported in the multiciliated ependymal cells that line the surface of brain ventricles. However, little is known about the cellular and molecular mechanisms by which this polarity is established. Here, we report in mice that basal bodies move in the apical cell membrane during differentiation to accumulate in the anterior region of ependymal cells. The planar cell polarity signaling pathway influences basal body orientation, but not their anterior migration, in the neonatal brain. Moreover, we show by pharmacological and genetic studies that non-muscle myosin II is a key regulator of this distribution of basal bodies. This study demonstrates that the orientation and distribution of basal bodies occur by distinct mechanisms.

  20. A Molecular Probe for the Detection of Polar Lipids in Live Cells

    PubMed Central

    Bader, Christie A.; Shandala, Tetyana; Carter, Elizabeth A.; Ivask, Angela; Guinan, Taryn; Hickey, Shane M.; Werrett, Melissa V.; Wright, Phillip J.; Simpson, Peter V.; Stagni, Stefano; Voelcker, Nicolas H.; Lay, Peter A.; Massi, Massimiliano; Brooks, Douglas A.

    2016-01-01

    Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular

  1. A Molecular Probe for the Detection of Polar Lipids in Live Cells.

    PubMed

    Bader, Christie A; Shandala, Tetyana; Carter, Elizabeth A; Ivask, Angela; Guinan, Taryn; Hickey, Shane M; Werrett, Melissa V; Wright, Phillip J; Simpson, Peter V; Stagni, Stefano; Voelcker, Nicolas H; Lay, Peter A; Massi, Massimiliano; Plush, Sally E; Brooks, Douglas A

    2016-01-01

    Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular

  2. Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

    PubMed Central

    Sääf, Annika M.; Halbleib, Jennifer M.; Chen, Xin; Yuen, Siu Tsan; Leung, Suet Yi

    2007-01-01

    Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. PMID:17699589

  3. Apolar and polar solvation thermodynamics related to the protein unfolding process.

    PubMed Central

    Bakk, Audun; Høye, Johan S; Hansen, Alex

    2002-01-01

    Thermodynamics related to hydrated water upon protein unfolding is studied over a broad temperature range (5-125 degrees C). The hydration effect arising from the apolar interior is modeled as an increased number of hydrogen bonds between water molecules compared with bulk water. The corresponding contribution from the polar interior is modeled as a two-step process. First, the polar interior breaks hydrogen bonds in bulk water upon unfolding. Second, due to strong bonds between the polar surface and the nearest water molecules, we assume quantization using a simplified two-state picture. The heat capacity change upon hydration is compared with model compound data evaluated previously for 20 different proteins. We obtain good correspondence with the data for both the apolar and the polar interior. We note that the effective coupling constants for both models have small variations among the proteins we have investigated. PMID:11806913

  4. Plasticity of both planar cell polarity and cell identity during the development of Drosophila.

    PubMed

    Saavedra, Pedro; Vincent, Jean-Paul; Palacios, Isabel M; Lawrence, Peter A; Casal, José

    2014-02-11

    Drosophila has helped us understand the genetic mechanisms of pattern formation. Particularly useful have been those organs in which different cell identities and polarities are displayed cell by cell in the cuticle and epidermis (Lawrence, 1992; Bejsovec and Wieschaus, 1993; Freeman, 1997). Here we use the pattern of larval denticles and muscle attachments and ask how this pattern is maintained and renewed over the larval moult cycles. During larval growth each epidermal cell increases manyfold in size but neither divides nor dies. We follow individuals from moult to moult, tracking marked cells and find that, as cells are repositioned and alter their neighbours, their identities change to compensate and the pattern is conserved. Single cells adopting a new fate may even acquire a new polarity: an identified cell that makes a forward-pointing denticle in the first larval stage may make a backward-pointing denticle in the second and third larval stages. DOI: http://dx.doi.org/10.7554/eLife.01569.001.

  5. Spa2p Interacts with Cell Polarity Proteins and Signaling Components Involved in Yeast Cell Morphogenesis

    PubMed Central

    Sheu, Yi-Jun; Santos, Beatriz; Fortin, Nathalie; Costigan, Christine; Snyder, Michael

    1998-01-01

    The yeast protein Spa2p localizes to growth sites and is important for polarized morphogenesis during budding, mating, and pseudohyphal growth. To better understand the role of Spa2p in polarized growth, we analyzed regions of the protein important for its function and proteins that interact with Spa2p. Spa2p interacts with Pea2p and Bud6p (Aip3p) as determined by the two-hybrid system; all of these proteins exhibit similar localization patterns, and spa2Δ, pea2Δ, and bud6Δ mutants display similar phenotypes, suggesting that these three proteins are involved in the same biological processes. Coimmunoprecipitation experiments demonstrate that Spa2p and Pea2p are tightly associated with each other in vivo. Velocity sedimentation experiments suggest that a significant portion of Spa2p, Pea2p, and Bud6p cosediment, raising the possibility that these proteins form a large, 12S multiprotein complex. Bud6p has been shown previously to interact with actin, suggesting that the 12S complex functions to regulate the actin cytoskeleton. Deletion analysis revealed that multiple regions of Spa2p are involved in its localization to growth sites. One of the regions involved in Spa2p stability and localization interacts with Pea2p; this region contains a conserved domain, SHD-II. Although a portion of Spa2p is sufficient for localization of itself and Pea2p to growth sites, only the full-length protein is capable of complementing spa2 mutant defects, suggesting that other regions are required for Spa2p function. By using the two-hybrid system, Spa2p and Bud6p were also found to interact with components of two mitogen-activated protein kinase (MAPK) pathways important for polarized cell growth. Spa2p interacts with Ste11p (MAPK kinase [MEK] kinase) and Ste7p (MEK) of the mating signaling pathway as well as with the MEKs Mkk1p and Mkk2p of the Slt2p (Mpk1p) MAPK pathway; for both Mkk1p and Ste7p, the Spa2p-interacting region was mapped to the N-terminal putative regulatory domain

  6. T Cells' Immunological Synapses Induce Polarization of Brain Astrocytes In Vivo and In Vitro: A Novel Astrocyte Response Mechanism to Cellular Injury

    PubMed Central

    Barcia, Carlos; Sanderson, Nicholas S. R.; Barrett, Robert J.; Wawrowsky, Kolja; Kroeger, Kurt M.; Puntel, Mariana; Liu, Chunyan; Castro, Maria G.; Lowenstein, Pedro R.

    2008-01-01

    Background Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown. Findings Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes. Conclusions Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1

  7. Wdr1-mediated cell shape dynamics and cortical tension are essential for epidermal planar cell polarity

    PubMed Central

    Pasolli, H. Amalia; Chai, Sophia; Nikolova, Maria; Stokes, Nicole; Fuchs, Elaine

    2015-01-01

    During mouse development, core planar cell polarity (PCP) proteins become polarized in the epidermal plane to guide angling/morphogenesis of hair follicles. How PCP is established is poorly understood. Here, we identify a key role for Wdr1 (also known as Aip1), an F-actin-binding protein that enhances cofilin/destrin-mediated F-actin disassembly. We show that cofilin and destrin function redundantly in developing epidermis, but their combined depletion perturbs cell adhesion, cytokinesis, apicobasal polarity and PCP. Although Wdr1 depletion accentuates single-loss-of-cofilin/destrin phenotypes, alone it resembles core PCP mutations. Seeking a mechanism, we find that Wdr1 and cofilin/destrin-mediated actomyosin remodelling are essential for generating or maintaining cortical tension within the developing epidermal sheet and driving the cell shape and planar orientation changes that accompany establishment of PCP in mammalian epidermis. Our findings suggest intriguing evolutionary parallels but mechanistic modifications to the distal wing hinge-mediated mechanical forces that drive cell shape change and orient PCP in the Drosophila wing disc. PMID:25915128

  8. Gradients of phosphatidylserine contribute to plasma membrane charge localization and cell polarity in fission yeast

    PubMed Central

    Haupt, Armin; Minc, Nicolas

    2017-01-01

    Surface charges at the inner leaflet of the plasma membrane may contribute to regulate the surface recruitment of key signaling factors. Phosphatidylserine (PS) is an abundant charged lipid that may regulate charge distribution in different cell types. Here we characterize the subcellular distribution and function of PS in the rod-shaped, polarized fission yeast. We find that PS preferably accumulates at cell tips and defines a gradient of negative charges along the cell surface. This polarization depends on actin-mediated endocytosis and contributes to the subcellular partitioning of charged polarity-regulating Rho GTPases like Rho1 or Cdc42 in a protein charge–dependent manner. Cells depleted of PS have altered cell dimensions and fail to properly regulate growth from the second end, suggesting a role for PS and membrane charge in polarized cell growth. PMID:27852900

  9. Polarized electroabsorption spectra and light soaking of solar cells based on hydrogenated amorphous silicon

    NASA Astrophysics Data System (ADS)

    Jiang, Lin; Wang, Qi; Schiff, E. A.; Guha, S.; Yang, J.

    1998-03-01

    We present grazing-incidence measurements of polarized electroabsorption spectra in p-i-n solar cells based on hydrogenated amorphous silicon (a-Si:H). We find a significantly stronger polarization dependence in the present measurements compared with earlier work based on electroabsorption detected using coplanar electrodes on a-Si:H thin films. We do not find any significant dependence of the polarized electroabsorption upon light soaking, although this effect was found in previous work with coplanar electrodes.

  10. Terrestrial photovoltaic cell process testing

    NASA Technical Reports Server (NTRS)

    Burger, D. R.

    1985-01-01

    The paper examines critical test parameters, criteria for selecting appropriate tests, and the use of statistical controls and test patterns to enhance PV-cell process test results. The coverage of critical test parameters is evaluated by examining available test methods and then screening these methods by considering the ability to measure those critical parameters which are most affected by the generic process, the cost of the test equipment and test performance, and the feasibility for process testing.

  11. Laminins in Epithelial Cell Polarization: Old Questions in Search of New Answers.

    PubMed

    Matlin, Karl S; Myllymäki, Satu-Marja; Manninen, Aki

    2017-02-03

    Laminin, a basement membrane protein discovered in 1979, was shortly thereafter implicated in the polarization of epithelial cells in both mammals and a variety of lower organisms. To transduce a spatial cue to the intrinsic polarization machinery, laminin must polymerize into a dense network that forms the foundation of the basement membrane. Evidence suggests that activation of the small GTPase Rac1 by β1-integrins mobilizes laminin-binding integrins and dystroglycan to consolidate formation of the laminin network and initiate rearrangements of both the actin and microtubule cytoskeleton to help establish the apicobasal axis. A key coordinator of spatial signals from laminin is the serine-threonine kinase Par-1, which is known to affect dystroglycan availability, microtubule and actin organization, and lumen formation. The signaling protein integrin-linked kinase (ILK) may also play a role. Despite significant advances, knowledge of the mechanism by which assembled laminin produces a spatial signal remains fragmentary, and much more research into the complex functions of laminin in polarization and other cellular processes is needed.

  12. Novel role for the midbody in primary ciliogenesis by polarized epithelial cells

    PubMed Central

    Bernabé-Rubio, Miguel; Fernández-Barrera, Jaime; Reglero-Real, Natalia; Fernández, José J.; Millán, Jaime; Correas, Isabel; Miguez, David G.

    2016-01-01

    The primary cilium is a membrane protrusion that is crucial for vertebrate tissue homeostasis and development. Here, we investigated the uncharacterized process of primary ciliogenesis in polarized epithelial cells. We show that after cytokinesis, the midbody is inherited by one of the daughter cells as a remnant that initially locates peripherally at the apical surface of one of the daughter cells. The remnant then moves along the apical surface and, once proximal to the centrosome at the center of the apical surface, enables cilium formation. The physical removal of the remnant greatly impairs ciliogenesis. We developed a probabilistic cell population–based model that reproduces the experimental data. In addition, our model explains, solely in terms of cell area constraints, the various observed transitions of the midbody, the beginning of ciliogenesis, and the accumulation of ciliated cells. Our findings reveal a biological mechanism that links the three microtubule-based organelles—the midbody, the centrosome, and the cilium—in the same cellular process. PMID:27458130

  13. Polarization of NK cell cytoskeleton upon conjugation with sensitive target cells.

    PubMed

    Carpén, O; Virtanen, I; Lehto, V P; Saksela, E

    1983-12-01

    We studied the cytoskeletal changes in natural killer (NK) cells during conjugate formation, i.e., when NK cells make contact with sensitive vs resistant target cells. F-actin and vinculin were seen to polarize at the contact sites upon conjugation with sensitive K562 cells, whereas in conjugates with resistant Raji target cells such an orientation was an infrequent finding. Myosin and two other cytoskeletal proteins, spectrin and vimentin, on the other hand, showed a random distribution in conjugating NK cells regardless of the target cell type. Hence the cytoskeletal redistribution associated with conjugation seems to be different from the receptor capping phenomenon, which is accompanied by clustering of actin, myosin, vimentin, and spectrin. On the basis of these results it seems probable that the lytic conjugate formation in NK-mediated cytotoxicity is associated with the formation of a specific type of junction that involves actin and vinculin. This cytoskeletal reorganization precedes and could be a prerequisite for the polarization of the cellular secretory apparatus and may be functionally responsible for the required cytokinetic movements.

  14. Integrins in epithelial cell polarity: using antibodies to analyze adhesive function and morphogenesis.

    PubMed

    Matlin, Karl S; Haus, Brian; Zuk, Anna

    2003-07-01

    Epithelial cells polarize in response to cell-substratum and cell-cell adhesive interactions. Contacts between cells and proteins of the extracellular matrix are mediated by integrin receptors. Of the 24 recognized integrin heterodimers, epithelial cells typically express four or more distinct integrins, with the exact complement dependent on the tissue of origin. Investigation of the roles of integrins in epithelial cell polarization has depended on the use of function-blocking antibodies both to determine ligand specificity of individual integrins and to disrupt and redirect normal morphogenesis. In this article we describe techniques for employing function-blocking anti-integrin antibodies in adhesion assays of the polarized Madin-Darby canine kidney (MDCK) cell line and to demonstrate the involvement of beta1 integrins in collagen-induced tubulocyst formation. These techniques can be easily expanded to other antibodies and epithelial cell lines to characterize specific functions of individual integrins in epithelial morphogenesis.

  15. New circular polarization selective surface concepts based on the Pierrot cell using printed circuit technology

    NASA Astrophysics Data System (ADS)

    Lopez, Humberto Israel

    This M.A.Sc. thesis focuses on finding an alternative method of constructing a circular polarization selective surface (CPSS) based on the Pierrot cell using the standard printed circuit technology. This technique uses a folded flexible substrate, which enables the implementation of the 3D Pierrot cells on a single metal layer defined with precision printed circuit board techniques, without the need for metalized via holes. Different topologies of the CPSS are analyzed in order to make the CPSS more efficient in terms of bandwidth and independence on the direction of propagation of the incident wave. A left-hand CPSS is designed to illustrate the benefits of the proposed approach. The first approach is a simple Pierrot unit cell CPSS which is optimized to have good reflection and transmission coefficients. A prototype is built and then characterized in a test bench operating in the K-band. For the fabricated prototype, the transmission coefficients of plane waves at normal incidence in the right-hand and the left-hand circular polarizations are --0.48 dB and --24 dB respectively. The bandwidth for which the transmission coefficient of the incident left-handed incident wave is greater than --3 dB was of 17.6%. These results are in good agreement with simulations results obtained with HFSS. A second variant considered is a Pierrot cell with a series load in the middle segment. With this cell it is possible to equalize the frequencies giving a better operation in the right- and left-handed circular polarized waves. There is an improvement for the co-pol to cross-pol ratio for the RHCP waves of 10 dB at 20 GHz. The added load does not affect the performance for the left-hand circular polarization, as expected. The third modification is a Pierrot cell at 90 degrees. This cell is designed to allow the combination of two Pierrot cells working at different frequencies on the same substrate in order to increase the frequency bandwidth of the CPSS. Unfortunately, the axial

  16. Ligation of the cell surface receptor, CD46, alters T cell polarity and response to antigen presentation

    PubMed Central

    Oliaro, Jane; Pasam, Anupama; Waterhouse, Nigel J.; Browne, Kylie A.; Ludford-Menting, Mandy J.; Trapani, Joseph A.; Russell, Sarah M.

    2006-01-01

    Lymphocyte function in vivo is dictated by multiple external cues, but the integration of different signals is not well understood. Here, we show that competition for the axis of polarization dictates functional outcomes. We investigated the effect of ligation of the immunoregulatory cell surface receptor, CD46, on lymphocyte polarity during antigen presentation and cytotoxic effector function. Ligation of CD46 on human T cells prevented recruitment of the microtubule organizing center, CD3, and perforin to the interface with the antigen-presenting cell and caused a reduction in IFN-γ production. In human NK cells, similar changes in polarity induced by CD46 ligation inhibited the recruitment of the microtubule organizing center and perforin to the interface with target cells and correlated with reduced killing. These data indicate that external signals can alter lymphocyte polarization toward antigen-presenting cells or target cells, inhibiting lymphocyte function. PMID:17116876

  17. Ligation of the cell surface receptor, CD46, alters T cell polarity and response to antigen presentation.

    PubMed

    Oliaro, Jane; Pasam, Anupama; Waterhouse, Nigel J; Browne, Kylie A; Ludford-Menting, Mandy J; Trapani, Joseph A; Russell, Sarah M

    2006-12-05

    Lymphocyte function in vivo is dictated by multiple external cues, but the integration of different signals is not well understood. Here, we show that competition for the axis of polarization dictates functional outcomes. We investigated the effect of ligation of the immunoregulatory cell surface receptor, CD46, on lymphocyte polarity during antigen presentation and cytotoxic effector function. Ligation of CD46 on human T cells prevented recruitment of the microtubule organizing center, CD3, and perforin to the interface with the antigen-presenting cell and caused a reduction in IFN-gamma production. In human NK cells, similar changes in polarity induced by CD46 ligation inhibited the recruitment of the microtubule organizing center and perforin to the interface with target cells and correlated with reduced killing. These data indicate that external signals can alter lymphocyte polarization toward antigen-presenting cells or target cells, inhibiting lymphocyte function.

  18. Dishevelled is essential for neural connectivity and planar cell polarity in planarians.

    PubMed

    Almuedo-Castillo, Maria; Saló, Emili; Adell, Teresa

    2011-02-15

    The Wingless/Integrated (Wnt) signaling pathway controls multiple events during development and homeostasis. It comprises multiple branches, mainly classified according to their dependence on β-catenin activation. The Wnt/β-catenin branch is essential for the establishment of the embryonic anteroposterior (AP) body axis throughout the phylogenetic tree. It is also required for AP axis establishment during planarian regeneration. Wnt/β-catenin-independent signaling encompasses several different pathways, of which the most extensively studied is the planar cell polarity (PCP) pathway, which is responsible for planar polarization of cell structures within an epithelial sheet. Dishevelled (Dvl) is the hub of Wnt signaling because it regulates and channels the Wnt signal into every branch. Here, we analyze the role of Schmidtea mediterranea Dvl homologs (Smed-dvl-1 and Smed-dvl-2) using gene silencing. We demonstrate that in addition to a role in AP axis specification, planarian Dvls are involved in at least two different β-catenin-independent processes. First, they are essential for neural connectivity through Smed-wnt5 signaling. Second, Smed-dvl-2, together with the S. mediterranea homologs of Van-Gogh (Vang) and Diversin (Div), is required for apical positioning of the basal bodies of epithelial cells. These data represent evidence not only of the function of the PCP network in lophotrocozoans but of the involvement of the PCP core elements Vang and Div in apical positioning of the cilia.

  19. Dishevelled is essential for neural connectivity and planar cell polarity in planarians

    PubMed Central

    Almuedo-Castillo, Maria; Saló, Emili; Adell, Teresa

    2011-01-01

    The Wingless/Integrated (Wnt) signaling pathway controls multiple events during development and homeostasis. It comprises multiple branches, mainly classified according to their dependence on β-catenin activation. The Wnt/β-catenin branch is essential for the establishment of the embryonic anteroposterior (AP) body axis throughout the phylogenetic tree. It is also required for AP axis establishment during planarian regeneration. Wnt/β-catenin–independent signaling encompasses several different pathways, of which the most extensively studied is the planar cell polarity (PCP) pathway, which is responsible for planar polarization of cell structures within an epithelial sheet. Dishevelled (Dvl) is the hub of Wnt signaling because it regulates and channels the Wnt signal into every branch. Here, we analyze the role of Schmidtea mediterranea Dvl homologs (Smed-dvl-1 and Smed-dvl-2) using gene silencing. We demonstrate that in addition to a role in AP axis specification, planarian Dvls are involved in at least two different β-catenin–independent processes. First, they are essential for neural connectivity through Smed-wnt5 signaling. Second, Smed-dvl-2, together with the S. mediterranea homologs of Van-Gogh (Vang) and Diversin (Div), is required for apical positioning of the basal bodies of epithelial cells. These data represent evidence not only of the function of the PCP network in lophotrocozoans but of the involvement of the PCP core elements Vang and Div in apical positioning of the cilia. PMID:21282632

  20. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

    PubMed

    Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

    2017-02-01

    Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

  1. Differentiation, polarization, and migration of human induced pluripotent stem cell-derived neural progenitor cells co-cultured with a human glial cell line with radial glial-like characteristics.

    PubMed

    Bamba, Yohei; Shofuda, Tomoko; Kanematsu, Daisuke; Nonaka, Masahiro; Yamasaki, Mami; Okano, Hideyuki; Kanemura, Yonehiro

    2014-05-16

    Here we established a unique human glial cell line, GDC90, derived from a human glioma and demonstrated its utility as a glial scaffold for the polarization and differentiation of human induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs). When co-cultured with GDC90 cells, iPSC-NPCs underwent rapid polarization and neurite extension along the radially spreading processes of the GDC90 cells, and showed migratory behavior. This method is potentially useful for detailed examination of neurites or for controlling neurites behavior for regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The use of syntaxin chimeras to study polarized protein trafficking in epithelial cells.

    PubMed

    ter Beest, Martin B A

    2008-01-01

    The plasma membrane of epithelial cells has two physically separated membrane domains. This membrane polarization is essential for the function of epithelial cells. It has been well established that different plasma membrane syntaxin forms are expressed in epithelial cells. In addition, these syntaxin forms can have a polarized localization, suggesting that they may play a direct role in the specificity of polarized membrane delivery. To determine the mechanism of the polarized syntaxin localization, we have made several chimeras of syntaxin 3 and 4. This allowed us to identify the protein sequences involved in this polarized localization. Using this technique, we showed that targeting information of syntaxin 3 and 4 is located in the first 30 amino acids.

  3. A Localized Complex of Two Protein Oligomers Controls the Orientation of Cell Polarity.

    PubMed

    Perez, Adam M; Mann, Thomas H; Lasker, Keren; Ahrens, Daniel G; Eckart, Michael R; Shapiro, Lucy

    2017-02-28

    Signaling hubs at bacterial cell poles establish cell polarity in the absence of membrane-bound compartments. In the asymmetrically dividing bacterium Caulobacter crescentus, cell polarity stems from the cell cycle-regulated localization and turnover of signaling protein complexes in these hubs, and yet the mechanisms that establish the identity of the two cell poles have not been established. Here, we recapitulate the tripartite assembly of a cell fate signaling complex that forms during the G1-S transition. Using in vivo and in vitro analyses of dynamic polar protein complex formation, we show that a polymeric cell polarity protein, SpmX, serves as a direct bridge between the PopZ polymeric network and the cell fate-directing DivJ histidine kinase. We demonstrate the direct binding between these three proteins and show that a polar microdomain spontaneously assembles when the three proteins are coexpressed heterologously in an Escherichia coli test system. The relative copy numbers of these proteins are essential for complex formation, as overexpression of SpmX in Caulobacter reorganizes the polarity of the cell, generating ectopic cell poles containing PopZ and DivJ. Hierarchical formation of higher-order SpmX oligomers nucleates new PopZ microdomain assemblies at the incipient lateral cell poles, driving localized outgrowth. By comparison to self-assembling protein networks and polar cell growth mechanisms in other bacterial species, we suggest that the cooligomeric PopZ-SpmX protein complex in Caulobacter illustrates a paradigm for coupling cell cycle progression to the controlled geometry of cell pole establishment.IMPORTANCE Lacking internal membrane-bound compartments, bacteria achieve subcellular organization by establishing self-assembling protein-based microdomains. The asymmetrically dividing bacterium Caulobacter crescentus uses one such microdomain to link cell cycle progression to morphogenesis, but the mechanism for the generation of this

  4. A Localized Complex of Two Protein Oligomers Controls the Orientation of Cell Polarity

    PubMed Central

    Lasker, Keren; Ahrens, Daniel G.; Eckart, Michael R.

    2017-01-01

    ABSTRACT Signaling hubs at bacterial cell poles establish cell polarity in the absence of membrane-bound compartments. In the asymmetrically dividing bacterium Caulobacter crescentus, cell polarity stems from the cell cycle-regulated localization and turnover of signaling protein complexes in these hubs, and yet the mechanisms that establish the identity of the two cell poles have not been established. Here, we recapitulate the tripartite assembly of a cell fate signaling complex that forms during the G1-S transition. Using in vivo and in vitro analyses of dynamic polar protein complex formation, we show that a polymeric cell polarity protein, SpmX, serves as a direct bridge between the PopZ polymeric network and the cell fate-directing DivJ histidine kinase. We demonstrate the direct binding between these three proteins and show that a polar microdomain spontaneously assembles when the three proteins are coexpressed heterologously in an Escherichia coli test system. The relative copy numbers of these proteins are essential for complex formation, as overexpression of SpmX in Caulobacter reorganizes the polarity of the cell, generating ectopic cell poles containing PopZ and DivJ. Hierarchical formation of higher-order SpmX oligomers nucleates new PopZ microdomain assemblies at the incipient lateral cell poles, driving localized outgrowth. By comparison to self-assembling protein networks and polar cell growth mechanisms in other bacterial species, we suggest that the cooligomeric PopZ-SpmX protein complex in Caulobacter illustrates a paradigm for coupling cell cycle progression to the controlled geometry of cell pole establishment. PMID:28246363

  5. Selective functionalization of nanofiber scaffolds to regulate salivary gland epithelial cell proliferation and polarity

    PubMed Central

    Cantara, Shraddha I.; Soscia, David A.; Sequeira, Sharon; Jean-Gilles, Riffard; Castracane, James; Larsen, Melinda

    2012-01-01

    Epithelial cell types typically lose apicobasal polarity when cultured on 2D substrates, but apicobasal polarity is required for directional secretion by secretory cells, such as salivary gland acinar cells. We cultured salivary gland epithelial cells on poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds that mimic the basement membrane, a specialized extracellular matrix, and examined cell proliferation and apicobasal polarization. Although cells proliferated on nanofibers, chitosan-coated nanofiber scaffolds stimulated proliferation of salivary gland epithelial cells. Although apicobasal cell polarity was promoted by the nanofiber scaffolds relative to flat surfaces, as determined by the apical localization of ZO-1, it was antagonized by the presence of chitosan. Neither salivary gland acinar nor ductal cells fully polarized on the nanofiber scaffolds, as determined by the homogenous membrane distribution of the mature tight junction marker, occludin. However, nanofiber scaffolds chemically functionalized with the basement membrane protein, laminin-111, promoted more mature tight junctions, as determined by apical localization of occludin but did not affect cell proliferation. To emulate the multifunctional capabilities of the basement membrane, bifunctional PLGA nanofibers were generated. Both acinar and ductal cell lines responded to signals provided by bifunctional scaffolds coupled to chitosan and laminin-111, demonstrating the applicability of such scaffolds for epithelial cell types. PMID:22938763

  6. Polarity governed selective amplification of through plane proton shuttling in proton exchange membrane fuel cells.

    PubMed

    Gautam, Manu; Chattanahalli Devendrachari, Mruthyunjayachari; Thimmappa, Ravikumar; Raja Kottaichamy, Alagar; Pottachola Shafi, Shahid; Gaikwad, Pramod; Makri Nimbegondi Kotresh, Harish; Ottakam Thotiyl, Musthafa

    2017-03-15

    Graphene oxide (GO) anisotropically conducts protons with directional dominance of in plane ionic transport (σ IP) over the through plane (σ TP). In a typical H2-O2 fuel cell, since the proton conduction occurs through the plane during its generation at the fuel electrode, it is indeed inevitable to selectively accelerate GO's σ TP for advancement towards a potential fuel cell membrane. We successfully achieved ∼7 times selective amplification of GO's σ TP by tuning the polarity of the dopant molecule in its nanoporous matrix. The coexistence of strongly non-polar and polar domains in the dopant demonstrated a synergistic effect towards σ TP with the former decreasing the number of water molecules coordinated to protons by ∼3 times, diminishing the effects of electroosmotic drag exerted on ionic movements, and the latter selectively accelerating σ TP across the catalytic layers by bridging the individual GO planes via extensive host guest H-bonding interactions. When they are decoupled, the dopant with mainly non-polar or polar features only marginally enhances the σ TP, revealing that polarity factors contribute to fuel cell relevant transport properties of GO membranes only when they coexist. Fuel cell polarization and kinetic analyses revealed that these multitask dopants increased the fuel cell performance metrics of the power and current densities by ∼3 times compared to the pure GO membranes, suggesting that the functional group factors of the dopants are of utmost importance in GO-based proton exchange membrane fuel cells.

  7. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion.

    PubMed

    Mojallal, Mahdi; Zheng, Yujuan; Hultin, Sara; Audebert, Stéphane; van Harn, Tanja; Johnsson, Per; Lenander, Claes; Fritz, Nicolas; Mieth, Christin; Corcoran, Martin; Lembo, Frédérique; Hallström, Marja; Hartman, Johan; Mazure, Nathalie M; Weide, Thomas; Grandér, Dan; Borg, Jean-Paul; Uhlén, Per; Holmgren, Lars

    2014-08-01

    The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

  8. A Comparison of Mathematical Models for Polarization of Single Eukaryotic Cells in Response to Guided Cues

    PubMed Central

    Jilkine, Alexandra; Edelstein-Keshet, Leah

    2011-01-01

    Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant) in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons), and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness. PMID:21552548

  9. von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells

    PubMed Central

    Lopes da Silva, Mafalda

    2016-01-01

    The von Willebrand factor (VWF) synthesized and secreted by endothelial cells is central to hemostasis and thrombosis, providing a multifunctional adhesive platform that brings together components needed for these processes. VWF secretion can occur from both apical and basolateral sides of endothelial cells, and from constitutive, basal, and regulated secretory pathways, the latter two via Weibel-Palade bodies (WPB). Although the amount and structure of VWF is crucial to its function, the extent of VWF release, multimerization, and polarity of the 3 secretory pathways have only been addressed separately, and with conflicting results. We set out to clarify these relationships using polarized human umbilical vein endothelial cells (HUVECs) grown on Transwell membranes. We found that regulated secretion of ultra–large (UL)-molecular-weight VWF predominantly occurred apically, consistent with a role in localized platelet capture in the vessel lumen. We found that constitutive secretion of low-molecular-weight (LMW) VWF is targeted basolaterally, toward the subendothelial matrix, using the adaptor protein complex 1 (AP-1), where it may provide the bulk of collagen-bound subendothelial VWF. We also found that basally-secreted VWF is composed of UL-VWF, released continuously from WPBs in the absence of stimuli, and occurs predominantly apically, suggesting this could be the main source of circulating plasma VWF. Together, we provide a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive, basal, and regulated pathways in polarized HUVECs, and have established a new role for AP-1 in the basolateral constitutive secretion of VWF. PMID:27106123

  10. Enhanced plasmid DNA utilization in transiently transfected CHO-DG44 cells in the presence of polar solvents.

    PubMed

    Rajendra, Yashas; Balasubramanian, Sowmya; Kiseljak, Divor; Baldi, Lucia; Wurm, Florian M; Hacker, David L

    2015-01-01

    Although the protein yields from transient gene expression (TGE) with Chinese hamster ovary (CHO) cells have recently improved, the amount of plasmid DNA (pDNA) needed for transfection remains relatively high. We describe a strategy to reduce the pDNA amount by transfecting CHO-DG44 cells with 0.06 μg pDNA/10(6) cells (10% of the optimal amount) in the presence of nonspecific (filler) DNA and various polar solvents including dimethylsufoxide, dimethyl formamide, acetonitrile, dimethyl acetamide (DMA), and hexamethyl phosphoramide (HMP). All of the polar solvents with the exception of HMP increased the production of a recombinant antibody in comparison to the untreated control transfection. In the presence of 0.25% DMA, the antibody yield in a 7-day batch culture was 500 mg/L. This was fourfold higher than the yield from the untreated control transfection. Mechanistic studies revealed that the polar solvents did not affect polyethylenimine-mediated pDNA delivery into cells or nuclei. The steady-state transgene mRNA level was elevated in the presence of each of the polar solvents tested, while the transgene mRNA half-life remained the same. These results indicated that the polar solvents enhanced transgene transcription. When screening a panel of recombinant antibodies and Fc-fusion proteins for production in the presence of the polar solvents, the highest increase in yield was observed following DMA addition for 11 of the 12 proteins. These results are expected to enhance the applicability of high-yielding TGE processes with CHO-DG44 cells by decreasing the amount of pDNA required for transfection.

  11. Theoretical estimate on tensor-polarization asymmetry in proton-deuteron Drell-Yan process

    NASA Astrophysics Data System (ADS)

    Kumano, S.; Song, Qin-Tao

    2016-09-01

    Tensor-polarized parton distribution functions are new quantities in spin-1 hadrons such as the deuteron, and they could probe new quark-gluon dynamics in hadron and nuclear physics. In charged-lepton deep inelastic scattering, they are studied by the twist-2 structure functions b1 and b2. The HERMES Collaboration found unexpectedly large b1 values compared to a naive theoretical expectation based on the standard deuteron model. The situation should be significantly improved in the near future by an approved experiment to measure b1 at Thomas Jefferson National Accelerator Facility (JLab). There is also an interesting indication in the HERMES result that finite antiquark tensor polarization exists. It could play an important role in solving a mechanism on tensor structure in the quark-gluon level. The tensor-polarized antiquark distributions are not easily determined from the charged-lepton deep inelastic scattering; however, they can be measured in a proton-deuteron Drell-Yan process with a tensor-polarized deuteron target. In this article, we estimate the tensor-polarization asymmetry for a possible Fermilab Main-Injector experiment by using optimum tensor-polarized parton distribution functions to explain the HERMES measurement. We find that the asymmetry is typically a few percent. If it is measured, it could probe new hadron physics, and such studies could create an interesting field of high-energy spin physics. In addition, we find that a significant tensor-polarized gluon distribution should exist due to Q2 evolution, even if it were zero at a low Q2 scale. The tensor-polarized gluon distribution has never been observed, so it is an interesting future project.

  12. Dkk-1 Inhibits Intestinal Epithelial Cell Migration by Attenuating Directional Polarization of Leading Edge Cells

    PubMed Central

    Koch, Stefan; Capaldo, Christopher T.; Samarin, Stanislav; Nava, Porfirio; Neumaier, Irmgard; Skerra, Arne; Sacks, David B.; Parkos, Charles A.

    2009-01-01

    Wnt signaling pathways regulate proliferation, motility, and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted Wnt antagonist that has been proposed to regulate tissue homeostasis in the intestine. In this report, we show that Dkk-1 is secreted by intestinal epithelial cells after wounding and that it inhibits cell migration by attenuating the directional orientation of migrating epithelial cells. Dkk-1 exposure induced mislocalized activation of Cdc42 in migrating cells, which coincided with a displacement of the polarity protein Par6 from the leading edge. Consequently, the relocation of the microtubule organizing center and the Golgi apparatus in the direction of migration was significantly and persistently inhibited in the presence of Dkk-1. Small interfering RNA-induced down-regulation of Dkk-1 confirmed that extracellular exposure to Dkk-1 was required for this effect. Together, these data demonstrate a novel role of Dkk-1 in the regulation of directional polarization of migrating intestinal epithelial cells, which contributes to the effect of Dkk-1 on wound closure in vivo. PMID:19776352

  13. Polar release of pathogenic Old World hantaviruses from renal tubular epithelial cells

    PubMed Central

    2012-01-01

    Background Epithelio- and endotheliotropic viruses often exert polarized entry and release that may be responsible for viral spread and dissemination. Hantaviruses, mostly rodent-borne members of the Bunyaviridae family infect epithelial and endothelial cells of different organs leading to organ dysfunction or even failure. Endothelial and renal epithelial cells belong to the target cells of Old World hantavirus. Therefore, we examined the release of hantaviruses in several renal epithelial cell culture models. We used Vero cells that are commonly used in hantavirus studies and primary human renal epithelial cells (HREpC). In addition, we analyzed MDCKII cells, an epithelial cell line of a dog kidney, which represents a widely accepted in vitro model of polarized monolayers for their permissiveness for hantavirus infection. Results Vero C1008 and primary HREpCs were grown on porous-support filter inserts for polarization. Monolayers were infected with hantavirus Hantaan (HTNV) and Puumala (PUUV) virus. Supernatants from the apical and basolateral chamber of infected cells were analyzed for the presence of infectious particles by re-infection of Vero cells. Viral antigen and infectious particles of HTNV and PUUV were exclusively detected in supernatants collected from the apical chamber of infected Vero C1008 cells and HREpCs. MDCKII cells were permissive for hantavirus infection and polarized MDCKII cells released infectious hantaviral particles from the apical surface corresponding to the results of Vero and primary human epithelial cells. Conclusions Pathogenic Old World hantaviruses are released from the apical surface of different polarized renal epithelial cells. We characterized MDCKII cells as a suitable polarized cell culture model for hantavirus infection studies. PMID:23194647

  14. Polar release of pathogenic Old World hantaviruses from renal tubular epithelial cells.

    PubMed

    Krautkrämer, Ellen; Lehmann, Maik J; Bollinger, Vanessa; Zeier, Martin

    2012-11-30

    Epithelio- and endotheliotropic viruses often exert polarized entry and release that may be responsible for viral spread and dissemination. Hantaviruses, mostly rodent-borne members of the Bunyaviridae family infect epithelial and endothelial cells of different organs leading to organ dysfunction or even failure. Endothelial and renal epithelial cells belong to the target cells of Old World hantavirus. Therefore, we examined the release of hantaviruses in several renal epithelial cell culture models. We used Vero cells that are commonly used in hantavirus studies and primary human renal epithelial cells (HREpC). In addition, we analyzed MDCKII cells, an epithelial cell line of a dog kidney, which represents a widely accepted in vitro model of polarized monolayers for their permissiveness for hantavirus infection. Vero C1008 and primary HREpCs were grown on porous-support filter inserts for polarization. Monolayers were infected with hantavirus Hantaan (HTNV) and Puumala (PUUV) virus. Supernatants from the apical and basolateral chamber of infected cells were analyzed for the presence of infectious particles by re-infection of Vero cells. Viral antigen and infectious particles of HTNV and PUUV were exclusively detected in supernatants collected from the apical chamber of infected Vero C1008 cells and HREpCs. MDCKII cells were permissive for hantavirus infection and polarized MDCKII cells released infectious hantaviral particles from the apical surface corresponding to the results of Vero and primary human epithelial cells. Pathogenic Old World hantaviruses are released from the apical surface of different polarized renal epithelial cells. We characterized MDCKII cells as a suitable polarized cell culture model for hantavirus infection studies.

  15. The influence of polar heterogeneous processes on reactive chlorine at middle latitudes - Three dimensional model implications

    NASA Technical Reports Server (NTRS)

    Douglass, Anne R.; Rood, Richard B.; Kaye, Jack A.; Stolarki, Richard S.; Allen, Dale J.

    1991-01-01

    Three-dimensional model calculations with the NASA/GSFC chemistry and transport model have been designed to consider the impact of heterogeneous processes occurring on polar stratospheric clouds (PSCs) in the Arctic vortex on the HCl distribution. By examining the HCl concentration for a calculation with PSCs relative to a calculation with gas phase chemistry only, the impact of polar processing on reactive chlorine species at middle latitudes is inferred. Results from the chemistry and transport model reproduce basic features of the ClO measurements (Toohey et al., 1991), which were made on the ferry flights of the ER-2 from Stavanger, Norway to Moffett Field, California via Wallops Island, Virginia on February 20 and 21, 1989. The model indicates that perturbed air which is contained within the polar vortex during winter is not homogeneously mixed, and that the ferry flights were made through air with the largest conversion of HCl to reactive chlorine that is seen at middle latitudes.

  16. Video image processing greatly enhances contrast, quality, and speed in polarization-based microscopy

    PubMed Central

    1981-01-01

    Video cameras with contrast and black level controls can yield polarized light and differential interference contrast microscope images with unprecedented image quality, resolution, and recording speed. The theoretical basis and practical aspects of video polarization and differential interference contrast microscopy are discussed and several applications in cell biology are illustrated. These include: birefringence of cortical structures and beating cilia in Stentor, birefringence of rotating flagella on a single bacterium, growth and morphogenesis of echinoderm skeletal spicules in culture, ciliary and electrical activity in a balancing organ of a nudibranch snail, and acrosomal reaction in activated sperm. PMID:6788777

  17. Polar/apolar compounds induce leukemia cell differentiation by modulating cell-surface potential.

    PubMed Central

    Arcangeli, A; Carlà, M; Del Bene, M R; Becchetti, A; Wanke, E; Olivotto, M

    1993-01-01

    The mechanism of action of polar/apolar inducers of cell differentiation, such as dimethyl sulfoxide and hexamethylene-bisacetamide, is still obscure. In this paper evidence is provided that their effects on murine erythroleukemia cells are modulated by various extracellular cations as a precise function of the cation effects on membrane surface potential. The interfacial effects of the inducers were directly measured on the charged electrode, showing that both dimethyl sulfoxide and hexamethylene-bisacetamide, at the effective concentrations for cell differentiation and within the physiological range of charge density, adsorb at the charged surface and produce a potential shift. A linear correlation was found between this shift and the inducer effects on cell differentiation. Besides offering a different interpretation of the mechanism of action of the inducers, these findings indicate that surface potential has a signaling function. They may also be relevant to cancer treatments based on tumor-cell commitment to terminal differentiation. Images Fig. 1 PMID:8516337

  18. Cell polarity-driven instability generates self-organized, fractal patterning of cell layers.

    PubMed

    Rudge, Timothy J; Federici, Fernán; Steiner, Paul J; Kan, Anton; Haseloff, Jim

    2013-12-20

    As a model system to study physical interactions in multicellular systems, we used layers of Escherichia coli cells, which exhibit little or no intrinsic coordination of growth. This system effectively isolates the effects of cell shape, growth, and division on spatial self-organization. Tracking the development of fluorescence-labeled cellular domains, we observed the emergence of striking fractal patterns with jagged, self-similar shapes. We then used a large-scale, cellular biophysical model to show that local instabilities due to polar cell-shape, repeatedly propagated by uniaxial growth and division, are responsible for generating this fractal geometry. Confirming this result, a mutant of E. coli with spherical shape forms smooth, nonfractal cellular domains. These results demonstrate that even populations of relatively simple bacterial cells can possess emergent properties due to purely physical interactions. Therefore, accurate physico-genetic models of cell growth will be essential for the design and understanding of genetically programmed multicellular systems.

  19. Planar cell polarity acts through septins to control collective cell movement and ciliogenesis.

    PubMed

    Kim, Su Kyoung; Shindo, Asako; Park, Tae Joo; Oh, Edwin C; Ghosh, Srimoyee; Gray, Ryan S; Lewis, Richard A; Johnson, Colin A; Attie-Bittach, Tania; Katsanis, Nicholas; Wallingford, John B

    2010-09-10

    The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease.

  20. Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis

    PubMed Central

    Kim, Su Kyoung; Shindo, Asako; Park, Tae Joo; Oh, Edwin C.; Ghosh, Srimoyee; Gray, Ryan S.; Lewis, Richard A.; Johnson, Colin A.; Attie-Bittach, Tania; Katsanis, Nicholas; Wallingford, John B.

    2012-01-01

    The planar cell polarity (PCP) signaling pathway governs collective cell movements duringvertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly ofcilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease. PMID:20671153

  1. Influenza virus hemagglutinin expression is polarized in cells infected with recombinant SV40 viruses carrying cloned hemagglutinin DNA.

    PubMed

    Roth, M G; Compans, R W; Giusti, L; Davis, A R; Nayak, D P; Gething, M J; Sambrook, J

    1983-06-01

    Primary cell cultures of African Green monkey kidney (AGMK) contain polarized epithelial cells in which influenza virus matures predominantly at the apical surfaces above tight junctions. Influenza virus glycoproteins were found to be localized at the same membrane domain from which the virus budded. When polarized primary AGMK cells were infected with recombinant SV40 viruses containing DNA coding for either an influenza virus H1 or H2 subtype hemagglutinin (HA), the HA proteins were preferentially expressed at the apical surface in a manner identical to that observed in influenza virus-infected cells. Thus, cellular mechanisms for sorting membrane glycoproteins recognize some structural feature of the HA glycoprotein itself, and other viral proteins are not necessary for this process.

  2. Wnt-Frizzled/Planar Cell Polarity Signaling: Cellular Orientation by Facing the Wind (Wnt)

    PubMed Central

    Yang, Yingzi; Mlodzik, Marek

    2015-01-01

    The establishment of planar cell polarity (PCP) in epithelial and mesenchymal cells is a critical, evolutionarily conserved process during development and organogenesis. Analyses in Drosophila and several vertebrate model organisms have contributed a wealth of information on the regulation of PCP. A key conserved pathway regulating PCP, the so-called core Wnt-Frizzled PCP (Fz/PCP) signaling pathway, was initially identified through genetic studies of Drosophila. PCP studies in vertebrates, most notably mouse and zebrafish, have identified novel factors in PCP signaling and have also defined cellular features requiring PCP signaling input. These studies have shifted focus to the role of Van Gogh (Vang)/Vangl genes in this molecular system. This review focuses on new insights into the core Fz/Vangl/PCP pathway and recent advances in Drosophila and vertebrate PCP studies. We attempt to integrate these within the existing core Fz/Vangl/PCP signaling framework. PMID:26566118

  3. Modeling Stem Cell Induction Processes

    PubMed Central

    Grácio, Filipe; Cabral, Joaquim; Tidor, Bruce

    2013-01-01

    Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important epigenetic regulatory features of DNA methylation and histone modification. We show that the network topology reported in the literature is consistent with the observed experimental behavior of bistability and inducibility. Based on simulations of stem cell generation protocols, and in particular focusing on changes in epigenetic cellular states, we show that cooperative and independent reaction mechanisms have experimentally identifiable differences in the dynamics of reprogramming, and we analyze such differences and their biological basis. It had been argued that stochastic and elite models of stem cell generation represent distinct fundamental mechanisms. Work presented here suggests an alternative possibility that they represent differences in the amount of information we have about the distribution of cellular states before and during reprogramming protocols. We show further that unpredictability and variation in reprogramming decreases as the cell progresses along the induction process, and that identifiable groups of cells with elite-seeming behavior can come about by a stochastic process. Finally we show how different mechanisms and kinetic properties impact the prospects of improving the efficiency of iPS cell generation protocols. PMID:23667423

  4. The Role of Eolian Processes in Forming Surface Features of the Martian Polar Layered Deposits

    NASA Astrophysics Data System (ADS)

    Howard, Alan D.

    2000-04-01

    The major topographic features of the martian polar layered deposits include the conspicuous spiral troughs, subtle undulations, broad reentrants (chasma), steep, arcuate scarps, and dune fields. A prominent role for eolian processes in the formation of all of these features is proposed. Strong katabatic winds occur on the north polar cap, producing widespread frost streaks. These cold drainage winds are analogous to those on the terrestrial Antarctic cap. In the chasmae convergent katabatic winds create yardangs and erode arcuate scarps in the layered deposits that are also the source for local dune fields migrating outward from the polar cap. The chasmae are postulated to originate by long-term erosion by katabatic wind. Wind plays a role in formation of the troughs and scarps primarily through removal of dust freed from exposed layered deposits by ablation of ice on defrosted equator-facing slopes. The undulations are created by interaction between surface erosion or deposition of perennial ice and standing waves in the shallow katabatic windflow. The south polar layered deposits exhibit topographic features similar to those at the north polar cap, but erosion and depositional processes creating these features may be inactive during the current epoch because of the lack of an extensive perennial ice cover and associated katabatic wind.

  5. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy

    PubMed Central

    Mucsi, Ashley D.; Meng, Junchen; Yan, Jiacong; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D.; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W.

    2017-01-01

    Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell–DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1–dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin–cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1–dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell–mediated DC suppression in a contact-dependent manner. PMID:28082358

  6. Polarization splitting phenomenon of photonic crystals constructed by two-fold rotationally symmetric unit-cells

    NASA Astrophysics Data System (ADS)

    Yasa, U. G.; Giden, I. H.; Turduev, M.; Kurt, H.

    2017-09-01

    We present an intrinsic polarization splitting characteristic of low-symmetric photonic crystals (PCs) formed by unit-cells with C 2 rotational symmetry. This behavior emerges from the polarization sensitive self-collimation effect for both transverse-magnetic (TM) and transverse-electric (TE) modes depending on the rotational orientations of the unit-cell elements. Numerical analyzes are performed in both frequency and time domains for different types of square lattice two-fold rotational symmetric PC structures. At incident wavelength of λ = 1550 nm, high polarization extinction ratios with ˜26 dB (for TE polarization) and ˜22 dB (for TM polarization) are obtained with an operating bandwidth of 59 nm. Moreover, fabrication feasibilities of the designed structure are analyzed to evaluate their robustness in terms of the unit-cell orientation: for the selected PC unit-cell composition, corresponding extinction ratios for both polarizations still remain to be over 18 dB for the unit-cell rotation interval of θ = [40°-55°]. Taking all these advantages, two-fold rotationally symmetric PCs could be considered as an essential component in photonic integrated circuits for polarization control of light.

  7. Cell polarity protein CRB3 is an independent favorable prognostic factor for clear cell renal cell carcinoma.

    PubMed

    Mao, Xiaona; Li, Pingping; Ren, Yu; Li, Juan; Zhou, Can; Yang, Jin; Liu, Peijun

    2015-02-01

    Epithelial cells possess apical‑basal polarity and loss of epithelial cell polarity contributes to tumorigenesis and cancer progression. The Crumbs (CRB) polarity protein plays a crucial role in epithelial polarity maintenance, apical membrane formation, and tissue morphogenesis. Although evidence is increasing on involvement of deregulated polarity proteins in cancers, little is currently known about the roles of the CRB (Drosophila), especially the roles of CRB3, a homolog of the CRB, in clear cell renal cell carcinoma (ccRCC). Studies have shown that CRB3 may act as a tumor suppressor in non‑human mammalian cells; the study here was aimed to examine the expression status of CRB3 in ccRCC and the relationships between CRB3 expression and clinicopathologic parameters of ccRCC patients. Our results showed that CRB3 was weakly expressed in ccRCC tissues, but strongly expressed in adjacent normal kidney tissues. Patients with loss of CRB3 expression showed a significantly shorter overall survival (OS) than patients with positive CRB3 expression. Our results suggested that CRB3 may be an independent favorable prognostic factor for patients with ccRCC. We also found that overexpression of CRB3 restrained invasion and migration of 786‑O cells and loss of CRB3 expression promoted invasion and migration of human embryonic kidney 293T (HEK 293T) cells. This finding may explain why the negative CRB3 expression was associated with poor prognosis in human ccRCC. Altogether, our data demonstrated that CRB3 may be used as a new independent favorable prognostic factor for human ccRCC.

  8. A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation.

    PubMed

    Ludford-Menting, Mandy J; Oliaro, Jane; Sacirbegovic, Faruk; Cheah, Eric T-Y; Pedersen, Natalie; Thomas, Suzanne J; Pasam, Anupama; Iazzolino, Rosa; Dow, Lukas E; Waterhouse, Nigel J; Murphy, Amanda; Ellis, Sarah; Smyth, Mark J; Kershaw, Michael H; Darcy, Phillip K; Humbert, Patrick O; Russell, Sarah M

    2005-06-01

    T cell shape is dictated by the selective recruitment of molecules to different regions of the cell (polarity) and is integral to every aspect of T cell function, from migration to cytotoxicity. This study describes a mechanism for the regulation of T cell polarity. We show that T cells contain a network of asymmetrically distributed proteins with the capacity to dictate the subcellular localization of both cell surface receptors and morphological determinants in T cells. Proteins from the Scribble, Crumbs3, and Par3 complexes, previously shown to regulate epithelial polarity, were polarized in T cells containing either uropods or immunological synapses. Reduction in Scribble expression prevented the polarization of cell surface receptors and prevented morphological changes associated with uropod formation, migration, and antigen presentation. By dynamically coordinating molecular distribution throughout the T cell, this network provides a mechanism by which T cell function and polarity are linked.

  9. Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

    PubMed Central

    Witte, Kristen; Strickland, Devin; Glotzer, Michael

    2017-01-01

    Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment. DOI: http://dx.doi.org/10.7554/eLife.26722.001 PMID:28682236

  10. Alternative cell polarity behaviours arise from changes in G-protein spatial dynamics.

    PubMed

    Chou, Ching-Shan; Moore, Travis I; Nie, Qing; Yi, Tau-Mu

    2015-04-01

    Yeast cells form a single mating projection when exposed to mating pheromone, a classic example of cell polarity. Prolonged treatment with pheromone or specific mutations results in alternative cell polarity behaviours. The authors performed mathematical modelling to investigate these unusual cell morphologies from the perspective of balancing spatial amplification (i.e. positive feedback that localises components) with spatial tracking (i.e. negative feedback that allows sensing of gradient). First, they used generic models of cell polarity to explore different cell polarity behaviours that arose from changes in the model spatial dynamics. By exploring the positive and negative feedback loops in each stage of a two-stage model, they simulated a variety of cell morphologies including single bending projections, single straight projections, periodic multiple projections and simultaneous double projections. In the second half of the study, they used a two-stage mechanistic model of yeast cell polarity focusing on G-protein signalling to integrate the modelling results more closely with the authors' previously published experimental observations. In summary, the combination of modelling and experiments describes how yeast cells exhibit a diversity of cell morphologies arising from two-stage G-protein signalling dynamics modulated by positive and negative feedbacks.

  11. Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo

    PubMed Central

    Meyen, Dana; Tarbashevich, Katsiaryna; Banisch, Torsten U; Wittwer, Carolina; Reichman-Fried, Michal; Maugis, Benoît; Grimaldi, Cecilia; Messerschmidt, Esther-Maria; Raz, Erez

    2015-01-01

    Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue. DOI: http://dx.doi.org/10.7554/eLife.05279.001 PMID:25875301

  12. Lower Stratospheric Temperature Differences In Meteorological Analyses and Their Impact On Polar Processing Studies

    NASA Astrophysics Data System (ADS)

    Manney, G.; Sabutis, J.; Pawson, S.; Santee, M.; Naujokat, B.; Swinbank, R.; Gelman, M.; Ebisuzaki, W.

    Models - chemical transport models (CTMs), trajectory and Eulerian transport mod- els, microphysical models - used in polar processing studies typically rely on winds and/or temperatures from one of several meteorological analyses to drive the transport and control processes such as polar stratospheric cloud (PSC) formation and chemical reaction rates. Using different analyzed data sets to obtain temperatures and temper- ature histories can have significant consequences. A quantitative comparison of six meteorological analyses (UK Met Office, National Centers for Environmental Pre- diction/Climate Prediction Center (NCEP), NCEP/National Center for Atmospheric Research Reanalysis (REAN), Freie Universität Berlin, European Centre for Medium- Range Weather Forecasts (ECMWF), NASA Data Assimilation Office (DAO)) is pre- sented for the cold 1999-2000 and 1995-1996 Arctic winters, showing substantial dif- ferences in diagnostics related to polar processing between the different analyses. Bi- ases between analyses vary from year to year. Temperature history case studies show substantial differences using Met Office, NCEP, REAN, ECMWF, and DAO analyses. Different meteorological conditions in the comparably cold winters of 1995-1996 and 1999-2000 had a large impact on both expectations for PSC formation and on the ef- fects of discrepancies between different meteorological analyses. Met Office, NCEP, REAN, ECMWF, and DAO analyses are commonly used in modeling polar processes; the choice of analysis can strongly influence the results of such studies.

  13. Wavefront curvature limitations and compensation to polar format processing for synthetic aperture radar images.

    SciTech Connect

    Doerry, Armin Walter

    2006-01-01

    Limitations on focused scene size for the Polar Format Algorithm (PFA) for Synthetic Aperture Radar (SAR) image formation are derived. A post processing filtering technique for compensating the spatially variant blurring in the image is examined. Modifications to this technique to enhance its robustness are proposed.

  14. The Variable Polarity Plasma Arc Welding Process: Its Application to the Space Shuttle External Tank

    NASA Technical Reports Server (NTRS)

    Nunes, A. C., Jr.; Bayless, E. O., Jr.; Wilson, W. A.

    1984-01-01

    This report describes progress in the implementation of the Variable Polarity Plasma Arc Welding (VPPAW) process at the External Tank (ET) assembly facility. Design allowable data has been developed for thicknesses up to 1.00 in. More than 24,000 in. of welding on liquid oxygen and liquid hydrogen cylinders has been made without an internal defect.

  15. Analysis of the interrelation between the processes of polarization and microstructuring in a magnetic fluid layer

    NASA Astrophysics Data System (ADS)

    Morozova, T. F.; Demin, M. S.

    2017-02-01

    The results of examining and analyzing the interrelation between the processes of polarization and structuring in magnetic fluid microlayers under the influence of the temperature, external electric and magnetic fields, and variations in the structure and amount of stabilizer have been presented.

  16. Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia.

    PubMed

    Dai, D; Li, L; Huebner, A; Zeng, H; Guevara, E; Claypool, D J; Liu, A; Chen, J

    2013-01-01

    Genes involved in the planar cell polarity (PCP) signaling pathway are essential for a number of developmental processes in mammals, such as convergent extension and ciliogenesis. Tissue-specific PCP effector genes of the PCP signaling pathway are believed to mediate PCP signals in a tissue- and cell type-specific manner. However, how PCP signaling controls the morphogenesis of mammalian tissues remains unclear. In this study, we investigated the role of inturned (Intu), a tissue-specific PCP effector gene, during hair follicle formation in mice. Tissue-specific disruption of Intu in embryonic epidermis resulted in hair follicle morphogenesis arrest because of the failure of follicular keratinocyte to differentiate. Targeting Intu in the epidermis resulted in almost complete loss of primary cilia in epidermal and follicular keratinocytes, and a suppressed hedgehog signaling pathway. Surprisingly, the epidermal stratification and differentiation programs and barrier function were not affected. These results demonstrate that tissue-specific PCP effector genes of the PCP signaling pathway control the differentiation of keratinocytes through the primary cilia in a cell fate- and context-dependent manner, which may be critical in orchestrating the propagation and interpretation of polarity signals