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Journal of Biochemistry Advance Access published online on March 13, 2008
Journal of Biochemistry, 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 Riveline, Evelyne Concord, Bastien Hermant, Thierry Vernet and Danièle Gulino-Debrac

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

1to whom correspondence should be addressed : Dr. Stephanie Bibert, Department of Pharmacology and Toxicology, Rue du Bugnon 27, 1005 Lausanne- Switzerland, Phone: 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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