Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling
Stephan Huveneers,Joppe Oldenburg,Emma Spanjaard,Gerard van der Krogt,Ilya Grigoriev,Anna Akhmanova,Holger Rehmann,Johan de Rooij +7 more
TLDR
A specialized subset of VE-cadherin adhesions senses cytoskeletal force and recruits Vinculin to control the stability of endothelial cell–cell junctions during their force-dependent remodeling.Abstract:
To remodel endothelial cell–cell adhesion, inflammatory cytokine- and angiogenic growth factor–induced signals impinge on the vascular endothelial cadherin (VE-cadherin) complex, the central component of endothelial adherens junctions. This study demonstrates that junction remodeling takes place at a molecularly and phenotypically distinct subset of VE-cadherin adhesions, defined here as focal adherens junctions (FAJs). FAJs are attached to radial F-actin bundles and marked by the mechanosensory protein Vinculin. We show that endothelial hormones vascular endothelial growth factor, tumor necrosis factor α, and most prominently thrombin induced the transformation of stable junctions into FAJs. The actin cytoskeleton generated pulling forces specifically on FAJs, and inhibition of Rho-Rock-actomyosin contractility prevented the formation of FAJs and junction remodeling. FAJs formed normally in cells expressing a Vinculin binding-deficient mutant of α-catenin, showing that Vinculin recruitment is not required for adherens junction formation. Comparing Vinculin-devoid FAJs to wild-type FAJs revealed that Vinculin protects VE-cadherin junctions from opening during their force-dependent remodeling. These findings implicate Vinculin-dependent cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis.read more
Citations
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Journal ArticleDOI
VE-Cadherin and Endothelial Adherens Junctions: Active Guardians of Vascular Integrity
TL;DR: Some of the most important pathways through which VE-cadherin modulates vascular homeostasis are reviewed and the emerging concepts in the overall biological role of this protein are discussed.
Journal ArticleDOI
Mechanics of epithelial tissue homeostasis and morphogenesis.
Charlène Guillot,Thomas Lecuit +1 more
TL;DR: The mechanical basis of tissue robustness and fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.
Journal ArticleDOI
E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch
Nicolas Borghi,Maria Sorokina,Olga G. Shcherbakova,William I. Weis,Beth L. Pruitt,W. James Nelson,Alexander R. Dunn +6 more
TL;DR: Findings point to a constitutive role of E-cadherin in transducing mechanical forces between the actomyosin cytoskeleton and the plasma membrane, not only at cell–cell junctions but throughout the cell surface.
Journal ArticleDOI
A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion
Anna Labernadie,Takuya Kato,Agustí Brugués,Xavier Serra-Picamal,Stefanie Derzsi,Esther N. Arwert,Anne Weston,Víctor González-Tarragó,Alberto Elosegui-Artola,Lorenzo Albertazzi,Jordi Alcaraz,Pere Roca-Cusachs,Erik Sahai,Xavier Trepat +13 more
TL;DR: The findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.
Journal ArticleDOI
The minimal cadherin-catenin complex binds to actin filaments under force
Craig D. Buckley,Jiongyi Tan,Karen L. Anderson,Dorit Hanein,Niels Volkmann,William I. Weis,W. James Nelson,Alexander R. Dunn,Alexander R. Dunn +8 more
TL;DR: The data and kinetic model reconcile previous in vitro and in vivo work by demonstrating that the cadherin-catenin complex binds robustly to actin filaments under force, and explains the mechanosensitivity of cadhersin-mediated intercellular adhesions.
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