Unraveling the distinct distributions of VE- and N-cadherins in endothelial cells: A key role for p120-catenin

• Published in: Experimental cell research Vol. 316; no. 16; pp. 2587 - 2599
• Main Authors: Gentil-dit-Maurin, Alice, Oun, Stella, Almagro, Sébastien, Bouillot, Stéphanie, Courçon, Marie, Linnepe, Ruth, Vestweber, Dietmar, Huber, Philippe, Tillet, Emmanuelle
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2010; Elsevier BV; Elsevier
• Subjects: Animals; Antigens, CD - metabolism; Binding sites; Blotting, Western; Cadherins - metabolism; Catenins - physiology; Cell Adhesion; Cell Behavior; Cell junctions; Cell Membrane - metabolism; Cells, Cultured; Cellular Biology; Cholesterol rafts; Comparative studies; Endothelial cells; Endothelium, Vascular - metabolism; Fluorescent Antibody Technique; Humans; Immunoprecipitation; Intercellular Junctions; Life Sciences; Lipids; Membrane Microdomains; Mice; Mice, Knockout; N-cadherin; Neovascularization, Physiologic; P120 ctn; Signal transduction; Umbilical Veins; VE-cadherin; Cholesterol rafts; N-cadherin; dpc; LR; p120 ctn; VE-cadherin; Cell junctions; HUVEC; siRNA; ES cells; EB; Endothelial cells
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.06.015

Endothelial cells express two different classical cadherins, vascular endothelial (VE) cadherin and neural (N) cadherin, having distinct functions in the vascular system. VE-cadherin is specific to endothelial adherens junctions and is strictly necessary for vascular morphogenesis. On the contrary, N-cadherin shows diffuse localization on the cell surface and interacts with mural cells for vessel stabilization. In this study, we sought to clarify the cellular mechanisms leading to the distinct cellular locations and functions of the two cadherins in the endothelium. VE-cadherin has been shown to be responsible for the junctional exclusion of N-cadherin. Using several endothelial models, we demonstrate that this property is dependent on VE-cadherin binding to p120 catenin (p120
ctn). Moreover, although in the absence of VE-cadherin N-cadherin can localize to cell contacts, angiogenesis remains impaired, demonstrating that endothelial junction formation is not sufficient for normal vessel development. Interestingly, we show that VE-cadherin, but not N-cadherin, is partially associated with cholesterol-enriched microdomains. Lipid raft-associated-VE-cadherin is characterized by a very high level of p120
ctn association, and this association is necessary for VE-cadherin recruitment into lipid rafts. Altogether, our results indicate a critical role for p120
ctn in regulating the membrane distribution of endothelial cadherins with functional consequences in terms of cadherin stabilization and intracellular signaling.