scholarly journals A Molecular Switch for the Orientation of Epithelial Cell Polarization

2014 ◽  
Vol 31 (2) ◽  
pp. 171-187 ◽  
Author(s):  
David M. Bryant ◽  
Julie Roignot ◽  
Anirban Datta ◽  
Arend W. Overeem ◽  
Minji Kim ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Molecular Switch ◽  
Cell Polarization

scholarly journals A bidirectional antagonism between aPKC and Yurt regulates epithelial cell polarity

2014 ◽  
Vol 204 (4) ◽  
pp. 487-495 ◽  
Author(s):  
Clémence L. Gamblin ◽  
Émilie J.-L. Hardy ◽  
François J.-M. Chartier ◽  
Nicolas Bisson ◽  
Patrick Laprise
Keyword(s):  
Epithelial Cell ◽  
Cell Polarity ◽  
Cell Polarization ◽  
Membrane Domains ◽  
Epithelial Cell Polarity ◽  
Kinase C ◽  
The Stability ◽  
Regulatory Loop ◽  
Late Stages ◽  
Apical Localization

During epithelial cell polarization, Yurt (Yrt) is initially confined to the lateral membrane and supports the stability of this membrane domain by repressing the Crumbs-containing apical machinery. At late stages of embryogenesis, the apical recruitment of Yrt restricts the size of the apical membrane. However, the molecular basis sustaining the spatiotemporal dynamics of Yrt remains undefined. In this paper, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical localization. A nonphosphorylatable version of Yrt dominantly dismantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell polarity. In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma membrane. The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity. Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulatory loop that contributes to segregation of distinct and mutually exclusive membrane domains in epithelial cells.

scholarly journals Girdin is a component of the lateral polarity protein network restricting cell dissemination

2019 ◽  
Author(s):  
Cornélia Biehler ◽  
Li-Ting Wang ◽  
Myriam Sévigny ◽  
Alexandra Jetté ◽  
Clémence Gamblin ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Polarity ◽  
Cancer Progression ◽  
Cell Polarization ◽  
Protein Network ◽  
Poor Overall Survival ◽  
Lung Cancers ◽  
Epithelial Cancers ◽  
Human Ortholog ◽  
Cell Dissemination

AbstractEpithelial cell polarity defects support cancer progression. It is thus crucial to decipher the functional interactions within the polarity protein network. Here we show that Drosophila Girdin and its human ortholog (GIRDIN) sustain the function of crucial lateral polarity proteins by inhibiting the apical kinase aPKC. Loss of GIRDIN expression is also associated with overgrowth of disorganized cell cysts. Moreover, we observed cell dissemination from GIRDIN knockdown cysts and tumorspheres, thereby showing that GIRDIN supports the cohesion of multicellular epithelial structures. Consistent with these observations, alteration of GIRDIN expression is associated with a poor overall survival in subtypes of breast and lung cancers. Overall, we discovered a core mechanism contributing to epithelial cell polarization from flies to humans. Our data also indicate that GIRDIN has the potential to impair the progression of epithelial cancers by preserving cell polarity and restricting cell dissemination.

Integrin expression and localization in normal MDCK cells and transformed MDCK cells lacking apical polarity

1994 ◽  
Vol 107 (2) ◽  
pp. 527-541 ◽  
Author(s):  
C.A. Schoenenberger ◽  
A. Zuk ◽  
G.M. Zinkl ◽  
D. Kendall ◽  
K.S. Matlin
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cell ◽  
Mdck Cells ◽  
Cell Polarization ◽  
Laminin Receptor ◽  
Apical Plasma Membrane ◽  
Epithelial Cell Line ◽  
Apical Polarity ◽  
Integrin Alpha 6 ◽  
Alpha V Beta 3

Epithelial cells polarize in response to contacts with the extracellular matrix and with neighboring cells. Interactions of cells with the extracellular matrix are mediated mainly by the integrin family of receptors. To begin to understand the role of integrins in polarization, we have investigated the expression and localization of three integrin families in the polarized Madin-Darby canine kidney (MDCK) epithelial cell line and in transformed MDCK cells lacking apical polarity. We find that MDCK cells express several beta 1 integrins, including alpha 2 beta 1, alpha 3 beta 1, and an unidentified integrin designated alpha × beta 1. The beta 1 integrins are the major receptors for collagens I and IV and laminin in MDCK cells, since a blocking anti-beta 1 antibody almost totally abolishes adhesion to these proteins. They also express a vitronectin receptor tentatively identified as alpha v beta 3, and the epithelial-specific integrin alpha 6 beta 4. The latter is not a laminin receptor in MDCK cells because a function blocking anti-alpha 6 antibody has no effect on cell adhesion to laminin. All three integrin families are expressed exclusively on both the basal and lateral surfaces, as determined by immunofluorescence microscopy and surface biotinylation. Transformed MDCK cells express beta 1 integrins as well as alpha v beta 3 and alpha 6 beta 4, but show alterations in the beta 1 family. Expression of alpha × is lacking, and the relative amount of the beta 1 subunit is diminished, resulting in the accumulation of Endo-H-sensitive alpha 3. In addition, surface biotinylation and immunofluorescence indicate that significant amounts of both alpha 2 beta 1 and alpha 3 beta 1 appear on not only the basolateral but also the apical plasma membrane. These results indicate that integrins are the major receptors for the extracellular matrix in MDCK cells, and that they may affect epithelial cell polarization by mediating not only cell-substratum but also cell-cell contacts.

scholarly journals An antiglycolipid antibody inhibits Madin-Darby canine kidney cell adhesion to laminin and interferes with basolateral polarization and tight junction formation.

1996 ◽  
Vol 133 (3) ◽  
pp. 695-708 ◽  
Author(s):  
G M Zinkl ◽  
A Zuk ◽  
P van der Bijl ◽  
G van Meer ◽  
K S Matlin
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Mdck Cells ◽  
Collagen Type I ◽  
Cell Polarization ◽  
Type I ◽  
Adhesion Protein ◽  
Tight Junction Formation ◽  
Extracellular Matrix Molecules

Epithelial cells polarize not only in response to cell-cell contacts, but also to contacts with a substratum composed of extracellular matrix molecules. To probe the role of specific matrix constituents in epithelial cell polarization, we investigated the effects of an adhesion-blocking mAb, 12B12, on initial polarization of MDCK cells. The 12B12 antibody, raised against whole MDCK cells, blocks adhesion to laminin by 65% but has no effect on adhesion of cells to collagen type I. Taking advantage of this antibody's function-blocking activity, as well as the fact that MDCK cells secrete laminin, the role of endogenous laminin in polarization was examined by plating cells on collagen-coated substrata in the presence of the antibody. Under these conditions, cell spreading was reduced 1.5h after plating, and cells were flatter and had fewer microvilli after 24 h. Even though lateral cell membranes were closely apposed, transepithelial resistance in the presence of the antibody was significantly reduced relative to controls. When the polarization of specific apical and basolateral markers was examined both biochemically and immunocytochemically in the presence of the antibody, we observed that the apical marker polarized at normal rates while basolateral markers did not. Surprisingly, the 12B12 antibody was not directed against any known cell adhesion protein but reacted specifically with Forssman antigen, a glycosphingolipid. These results suggest that glycolipids may play a significant role in cell adhesion via laminin and in epithelial cell polarization.

scholarly journals Apical targeting of syntaxin 3 is essential for epithelial cell polarity

2006 ◽  
Vol 173 (6) ◽  
pp. 937-948 ◽  
Author(s):  
Nikunj Sharma ◽  
Seng Hui Low ◽  
Saurav Misra ◽  
Bhattaram Pallavi ◽  
Thomas Weimbs
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cell ◽  
Membrane Trafficking ◽  
Cell Polarization ◽  
Apical Plasma Membrane ◽  
Membrane Expression ◽  
Tight Junction Formation ◽  
Necessary And Sufficient ◽  
Syntaxin 3

In polarized epithelial cells, syntaxin 3 localizes to the apical plasma membrane and is involved in membrane fusion of apical trafficking pathways. We show that syntaxin 3 contains a necessary and sufficient apical targeting signal centered around a conserved FMDE motif. Mutation of any of three critical residues within this motif leads to loss of specific apical targeting. Modeling based on the known structure of syntaxin 1 revealed that these residues are exposed on the surface of a three-helix bundle. Syntaxin 3 targeting does not require binding to Munc18b. Instead, syntaxin 3 recruits Munc18b to the plasma membrane. Expression of mislocalized mutant syntaxin 3 in Madin-Darby canine kidney cells leads to basolateral mistargeting of apical membrane proteins, disturbance of tight junction formation, and loss of ability to form an organized polarized epithelium. These results indicate that SNARE proteins contribute to the overall specificity of membrane trafficking in vivo, and that the polarity of syntaxin 3 is essential for epithelial cell polarization.

scholarly journals CRB3A Controls the Morphology and Cohesion of Cancer Cells through Ehm2/p114RhoGEF-Dependent Signaling

2015 ◽  
Vol 35 (19) ◽  
pp. 3423-3435 ◽  
Author(s):  
Elise Loie ◽  
Lucie E. Charrier ◽  
Kévin Sollier ◽  
Jean-Yves Masson ◽  
Patrick Laprise
Keyword(s):  
Epithelial Cell ◽  
Cancer Cells ◽  
Hela Cells ◽  
Cell Shape ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Transmembrane Protein ◽  
Cell Polarization ◽  
Cell Periphery ◽  
Mesenchymal Transition

The transmembrane protein CRB3A controls epithelial cell polarization. Elucidating the molecular mechanisms of CRB3A function is essential as this protein prevents the epithelial-to-mesenchymal transition (EMT), which contributes to tumor progression. To investigate the functional impact of altered CRB3A expression in cancer cells, we expressed CRB3A in HeLa cells, which are devoid of endogenous CRB3A. While control HeLa cells display a patchy F-actin distribution, CRB3A-expressing cells form a circumferential actomyosin belt. This reorganization of the cytoskeleton is accompanied by a transition from an ameboid cell shape to an epithelial-cell-like morphology. In addition, CRB3A increases the cohesion of HeLa cells. To perform these functions, CRB3A recruits p114RhoGEF and its activator Ehm2 to the cell periphery using both functional motifs of its cytoplasmic tail and increases RhoA activation levels. ROCK1 and ROCK2 (ROCK1/2), which are critical effectors of RhoA, are also essential to modulate the cytoskeleton and cell shape downstream of CRB3A. Overall, our study highlights novel roles for CRB3A and deciphers the signaling pathway conferring to CRB3A the ability to fulfill these functions. Thereby, our data will facilitate further investigation of CRB3A functions and increase our understanding of the cellular defects associated with the loss of CRB3A expression in cancer cells.

Mesenchyme-mediated effects of retinoic acid during rat intestinal development

1997 ◽  
Vol 110 (10) ◽  
pp. 1227-1238 ◽  
Author(s):  
M. Plateroti ◽  
J.N. Freund ◽  
C. Leberquier ◽  
M. Kedinger
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cell ◽  
Polyclonal Antibodies ◽  
Mesenchymal Cell ◽  
Mesenchymal Cells ◽  
Cell Polarization ◽  
Cell Interactions ◽  
Intestinal Cell ◽  
Cell Phenotype ◽  
Intestinal Development

In previous experiments we showed that intestinal development was dependent upon epithelial-mesenchymal cell interactions. The aim of this study was to investigate the possible role of retinoic acid (RA), a morphogenetic and differentiating agent, on the gut epithelial-mesenchymal unit. For this purpose we first analyzed the effects of a physiological dose of RA on 14-day fetal rat intestine using short-term organ culture experiments, or long-term grafts under the skin of nude mice. In these conditions, RA accelerated villus outgrowth and epithelial cell differentiation as assessed by the onset of lactase expression, and it also stimulated muscle and crypt formation. In order to analyze potential effects of RA mediated by mesenchymal cells, we isolated and characterized gut mucosa mesenchyme-derived cell cultures (mesenchyme-derived intestinal cell lines, MIC). These cells were shown to express mRNAs for retinoid binding proteins similar to those expressed in situ in the intestinal mesenchyme. MIC cells co-cultured with 14-day intestinal endoderms promoted endodermal cell adhesion and growth, and the addition of exogeneous RA enhanced epithelial cell polarization and differentiation assessed by cytokeratin and lactase immunostaining. Such a differentiating effect of RA was not observed on endodermal cells when cultured without a mesenchymal feeder layer or maintained in conditioned medium from RA-treated MIC cells. In the co-cultures, immunostaining of laminin and collagen IV with polyclonal antibodies, as well as alpha1 and beta1 laminin chains mRNAs (analyzed by RT-PCR) increased concurrently with the RA-enhanced differentiation of epithelial cells. It is worth noting that this stimulation by RA was also obvious on the mesenchymal cells cultured alone. These results show that RA plays a role in intestinal morphogenesis and differentiation. In addition, they indicate that RA acts on the mesenchymal cell phenotype and suggest that RA may modify the mesenchymal-epithelial cell interactions during intestinal development.

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