scholarly journals MAGI-1 Is Required for Rap1 Activation upon Cell-Cell Contact and for Enhancement of Vascular Endothelial Cadherin-mediated Cell Adhesion

2006 ◽  
Vol 17 (2) ◽  
pp. 966-976 ◽  
Author(s):  
Atsuko Sakurai ◽  
Shigetomo Fukuhara ◽  
Akiko Yamagishi ◽  
Keisuke Sako ◽  
Yuji Kamioka ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adherens Junction ◽  
Small Gtpase ◽  
Cell Contact ◽  
Vascular Endothelial ◽  
Nucleotide Exchange ◽  
Cell Contacts ◽  
Vascular Endothelial Cadherin ◽  
Rap1 Activation ◽  
Cell Cell

Rap1 is a small GTPase that regulates adherens junction maturation. It remains elusive how Rap1 is activated upon cell-cell contact. We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin (VE-cadherin) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin-dependent Rap1 activation. We found that MAGI-1 localized to cell-cell contacts presumably by associating with β-catenin and that MAGI-1 bound to a guanine nucleotide exchange factor for Rap1, PDZ-GEF1. Depletion of MAGI-1 suppressed the cell-cell contact-induced Rap1 activation and the VE-cadherin-mediated cell-cell adhesion after Ca2+ switch. In addition, relocation of vinculin from cell-extracellular matrix contacts to cell-cell contacts after the Ca2+ switch was inhibited in MAGI-1-depleted cells. Furthermore, inactivation of Rap1 by overexpression of Rap1GAPII impaired the VE-cadherin-dependent cell adhesion. Collectively, MAGI-1 is important for VE-cadherin-dependent Rap1 activation upon cell-cell contact. In addition, once activated, Rap1 upon cell-cell contacts positively regulate the adherens junction formation by relocating vinculin that supports VE-cadherin-based cell adhesion.

scholarly journals An Elmo–Dock complex locally controls Rho GTPases and actin remodeling during cadherin-mediated adhesion

2014 ◽  
Vol 207 (5) ◽  
pp. 577-587 ◽  
Author(s):  
Christopher P. Toret ◽  
Caitlin Collins ◽  
W. James Nelson
Keyword(s):  
Cell Adhesion ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Cell Contact ◽  
Nucleotide Exchange ◽  
Cell Contacts ◽  
Guanine Nucleotide Exchange ◽  
A Genome ◽  
Dependent Cell ◽  
Cell Cell

Cell–cell contact formation is a dynamic process requiring the coordination of cadherin-based cell–cell adhesion and integrin-based cell migration. A genome-wide RNA interference screen for proteins required specifically for cadherin-dependent cell–cell adhesion identified an Elmo–Dock complex. This was unexpected as Elmo–Dock complexes act downstream of integrin signaling as Rac guanine-nucleotide exchange factors. In this paper, we show that Elmo2 recruits Dock1 to initial cell–cell contacts in Madin–Darby canine kidney cells. At cell–cell contacts, both Elmo2 and Dock1 are essential for the rapid recruitment and spreading of E-cadherin, actin reorganization, localized Rac and Rho GTPase activities, and the development of strong cell–cell adhesion. Upon completion of cell–cell adhesion, Elmo2 and Dock1 no longer localize to cell–cell contacts and are not required subsequently for the maintenance of cell–cell adhesion. These studies show that Elmo–Dock complexes are involved in both integrin- and cadherin-based adhesions, which may help to coordinate the transition of cells from migration to strong cell–cell adhesion.

scholarly journals Rab35 regulates cadherin-mediated adherens junction formation and myoblast fusion

2013 ◽  
Vol 24 (3) ◽  
pp. 234-245 ◽  
Author(s):  
Sophie Charrasse ◽  
Franck Comunale ◽  
Sylvain De Rossi ◽  
Arnaud Echard ◽  
Cécile Gauthier-Rouvière
Keyword(s):  
Adherens Junction ◽  
Phosphatidyl Inositol ◽  
Myoblast Fusion ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Cell Contact ◽  
Dependent Manner ◽  
Cell Contacts ◽  
Contact Sites ◽  
Cell Cell

Cadherins are homophilic cell–cell adhesion molecules implicated in many fundamental processes, such as morphogenesis, cell growth, and differentiation. They accumulate at cell–cell contact sites and assemble into large macromolecular complexes named adherens junctions (AJs). Cadherin targeting and function are regulated by various cellular processes, many players of which remain to be uncovered. Here we identify the small GTPase Rab35 as a new regulator of cadherin trafficking and stabilization at cell–cell contacts in C2C12 myoblasts and HeLa cells. We find that Rab35 accumulates at cell–cell contacts in a cadherin-dependent manner. Knockdown of Rab35 or expression of a dominant-negative form of Rab35 impaired N- and M-cadherin recruitment to cell–cell contacts, their stabilization at the plasma membrane, and association with p120 catenin and led to their accumulation in transferrin-, clathrin-, and AP-2–positive intracellular vesicles. We also find that Rab35 function is required for PIP5KIγ accumulation at cell–cell contacts and phosphatidyl inositol 4,5-bisphosphate production, which is involved in cadherin stabilization at contact sites. Finally, we show that Rab35 regulates myoblast fusion, a major cellular process under the control of cadherin-dependent signaling. Taken together, these results reveal that Rab35 regulates cadherin-dependent AJ formation and myoblast fusion.

scholarly journals Vascular Endothelial Cadherin-mediated Cell-cell Adhesion Regulated by a Small GTPase, Rap1

BMB Reports ◽  
2006 ◽  
Vol 39 (2) ◽  
pp. 132-139 ◽  
Author(s):  
Shigetomo Fukuhra ◽  
Atsuko Sakurai ◽  
Akiko Yamagishi ◽  
Keisuke Sako ◽  
Naoki Mochizuki
Keyword(s):  
Cell Adhesion ◽  
Small Gtpase ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Cell Cell

scholarly journals Proline-rich Tyrosine Kinase 2 (Pyk2) Mediates Vascular Endothelial-Cadherin-based Cell-Cell Adhesion by Regulating β-Catenin Tyrosine Phosphorylation

2005 ◽  
Vol 280 (22) ◽  
pp. 21129-21136 ◽  
Author(s):  
Jaap D. van Buul ◽  
Eloise C. Anthony ◽  
Mar Fernandez-Borja ◽  
Keith Burridge ◽  
Peter L. Hordijk
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Tyrosine Kinase 2 ◽  
Cell Cell

scholarly journals N-Cadherin Association with Lipid Rafts Regulates Its Dynamic Assembly at Cell-Cell Junctions in C2C12 Myoblasts

2005 ◽  
Vol 16 (5) ◽  
pp. 2168-2180 ◽  
Author(s):  
Marie Causeret ◽  
Nicolas Taulet ◽  
Franck Comunale ◽  
Cyril Favard ◽  
Cécile Gauthier-Rouvière
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Cell Junctions ◽  
Cell Contact ◽  
C2c12 Myoblasts ◽  
Cell Contacts ◽  
Dynamic Assembly ◽  
Cell Cell

Cadherins are homophilic cell-cell adhesion molecules implicated in cell growth, differentiation, and organization into tissues during embryonic development. They accumulate at cell-cell contact sites and act as adhesion-activated signaling receptors. Here, we show that the dynamic assembly of N-cadherin at cell-cell contacts involves lipid rafts. In C2C12 myoblasts, immunofluorescence and biochemical experiments demonstrate that N-cadherin present at cell-cell contacts is colocalized with lipid rafts. Disruption of lipid rafts leads to the inhibition of cell-cell adhesion and disorganization of N-cadherin–dependent cell-cell contacts without modifying the association of N-cadherin with catenins and its availability at the plasma membrane. Fluorescent recovery after photobleaching experiments demonstrate that at the dorsal plasma membrane, lipid rafts are not directly involved in the diffusional mobility of N-cadherin. In contrast, at cell-cell junctions N-cadherin association with lipid rafts allows its stabilization enabling the formation of a functional adhesive complex. We show that lipid rafts, as homophilic interaction and F-actin association, stabilize cadherin-dependent adhesive complexes. Homophilic interactions and F-actin association of N-cadherin are both required for its association to lipid rafts. We thus identify lipid rafts as new regulators of cadherin-mediated cell adhesion.

scholarly journals Vascular Endothelial-Cadherin Stabilizes at Cell–Cell Junctions by Anchoring to Circumferential Actin Bundles through α- and β-Catenins in Cyclic AMP-Epac-Rap1 Signal-activated Endothelial Cells

2010 ◽  
Vol 21 (4) ◽  
pp. 584-596 ◽  
Author(s):  
Kazuomi Noda ◽  
Jianghui Zhang ◽  
Shigetomo Fukuhara ◽  
Satoshi Kunimoto ◽  
Michihiro Yoshimura ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Classical Model ◽  
Green Fluorescence Protein ◽  
Cell Junctions ◽  
Vascular Endothelial ◽  
Cell Contacts ◽  
Actin Bundles ◽  
Dependent Cell ◽  
A Cell ◽  
Cell Cell

Vascular endothelial (VE)-cadherin is a cell–cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin–dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell–cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell–cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, α-catenin, and β-catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of α- and β-catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that α-catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through α- and β-catenins are important for the stabilization of VE-cadherin at the cell–cell contacts in cAMP-Epac-Rap1 signal-activated cells.

scholarly journals Protein zero, a nervous system adhesion molecule, triggers epithelial reversion in host carcinoma cells.

1995 ◽  
Vol 131 (2) ◽  
pp. 465-482 ◽  
Author(s):  
J P Doyle ◽  
J G Stempak ◽  
P Cowin ◽  
D R Colman ◽  
D D'Urso
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Hela Cells ◽  
Adherens Junction ◽  
Cell Contact ◽  
Immunoglobulin Gene ◽  
Epithelial Junctions ◽  
Protein Zero ◽  
Cell Cell

Protein zero (P(o)) is the immunoglobulin gene superfamily glycoprotein that mediates the self-adhesion of the Schwann cell plasma membrane that yields compact myelin. HeLa is a poorly differentiated carcinoma cell line that has lost characteristic morphological features of the cervical epithelium from which it originated. Normally, HeLa cells are not self-adherent. However, when P(o) is artificially expressed in this line, cells rapidly aggregate, and P(o) concentrates specifically at cell-cell contact sites. Rows of desmosomes are generated at these interfaces, the plasma membrane localization of cingulin and ZO-1, proteins that have been shown to be associated with tight junctions, is substantially increased, and cytokeratins coalesce into a cohesive intracellular network. Immunofluorescence patterns for the adherens junction proteins N-cadherin, alpha-catenin, and vinculin, and the desmosomal polypeptides desmoplakin, desmocollin, and desmoglein, are also markedly enhanced at the cell surface. Our data demonstrate that obligatory cell-cell adhesion, which in this case is initially brought about by the homophilic association of P(o) molecules across the intercellular cleft, triggers pronounced augmentation of the normally sluggish or sub-basal cell adhesion program in HeLa cells, culminating in suppression of the transformed state and reversion of the monolayer to an epithelioid phenotype. Furthermore, this response is apparently accompanied by an increase in mRNA and protein levels for desmoplakin and N-cadherin which are normally associated with epithelial junctions. Our conclusions are supported by analyses of ten proteins we examined immunochemically (P(o), cingulin, ZO-1, desmoplakin, desmoglein, desmocollin, N-cadherin, alpha-catenin, vinculin, and cytokeratin-18), and by quantitative polymerase chain reactions to measure relative amounts of desmoplakin and N-cadherin mRNAs. P(o) has no known signaling properties; the dramatic phenotypic changes we observed are highly likely to have developed in direct response to P(o)-induced cell adhesion. More generally, the ability of this "foreign" membrane adhesion protein to stimulate desmosome and adherens junction formation by augmenting well-studied cadherin-based adhesion mechanisms raises the possibility that perhaps any bona fide cell adhesion molecule, when functionally expressed, can engage common intracellular pathways and trigger reversion of a carcinoma to an epithelial-like phenotype.

Vascular Endothelial Cadherin (VE-Cadherin): Cloning and Role in Endothelial Cell-Cell Adhesion

1997 ◽  
Vol 4 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Jahanara Ali ◽  
Fang Liao ◽  
Eric Martens ◽  
William A. Muller
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Cell Cell
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