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Journal of Biochemistry Advance Access originally published online on March 13, 2008
Journal of Biochemistry 2008 143(6):821-832; doi:10.1093/jb/mvn035
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© 2008 The Japanese Biochemical Society

Establishment of cell–cell junctions depends on the oligomeric states of VE-cadherin

Stéphanie Bibert1,*, Hélène Ayari2, Daniel Riveline2, Evelyne Concord1, Bastien Hermant1, Thierry Vernet1 and Danièle Gulino-Debrac1

1Laboratoire d’Ingénierie des Macromolécules, Institut de Biologie Structurale Jean-Pierre Ebel, (CEA/CNRS, UJF), 41 rue Jules Horowitz, 38027 Grenoble Cedex; and 2Laboratoire de Spectrométrie Physique, (CNRS/Université Joseph Fourier), 38402 Saint-Martin d'Hères Cedex, France

*To whom correspondence should be addressed. Tel: +41-21-692-54-26, Fax: +41-21-692-53-55, E-mail: Stephanie.Bibert{at}unil.ch

Received January 31, 2008; Accepted February 28, 2008


  Abstract

Specifically expressed at intercellular adherens junctions of endothelial cells, VE-cadherin is a receptor that exhibits particular self-association properties. Indeed, in vitro studies demonstrated that the extracellular part of VE-cadherin elaborates Ca++-dependent hexameric structures. We hypothesized that this assembly could be at the basis of a new cadherin-mediated cell–cell adhesion mechanism. To verify this assumption, we first demonstrated that VE-cadherin can elaborate hexamers at the cell surface of confluent endothelial cells. Second, mutations were introduced within the extracellular part of VE-cadherin to destabilize the hexamer. Following an in vitro screening, three mutants were selected, among which, one is able to elaborate only dimers. The selected mutations were expressed as C-terminal green fluorescent protein fusions in CHO cells. Despite their capacity to elaborate nascent cell–cell contacts, the mutants seem to be rapidly degraded and/or internalized. Altogether, our results suggest that the formation of VE-cadherin hexamers protects this receptor and might allow the elaboration of mature endothelial cell–cell junctions.

Key Words: adhesion, cell–cell junctions, endothelium, hexamer, VE-cadherin


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