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Alice Gentil Dit Maurin

Differential properties of N- and VE-cadherin in vascular endothelium



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Published on 2 July 2010
Thesis presented July 02, 2010

Abstract:
Endothelium integrity is maintained by junctional adhesion structures, in particular adherents junctions. Classical cadherins are the main molecule belonging to these structures. Two classical cadherins are expressed in the endothelium. First, the vascular endothelial cadherin or VE-cadherin​ is only expressed in endothelial cells and located to adherents junctions. Several studies have shown that this molecule is strictly necessary during vascular development. The second classical endothelial cadherin is represented by the neural cadherin or N-cadherin. Contrary to classical cadherins, the endothelial N-cadherin shows diffuse location on the entirely cell surface and interacts with mural cells for vessel stabilization. Moreover, its role in angiogenic process is still debated.
The purpose of our study was to decipher the differential role of N- and VE-cadherin in endothelial cells and during angiogenesis. We have shown that VE-cadherin was able to organize and displace N-cadherin location on the cell surface. Moreover, VE-cadherin binding to p120 catenin is required for N-cadherin junctional exclusion. Furthermore, endothelial lipid rafts, known to organize classical cadherin at the membrane, contain exclusively VE-cadherin, where it specifically binds p120 catenin. So, this protein complex could form a platform that stabilizes cadherin at the cell membrane and in the same way, strengthens intercellular interactions.
Also, we have found that three endothelial genes: PECAM, Flk-1 and Tie-2, could be transcriptionally controlled by VE-cadherin in a ES cell-derived endothelial differential model. We didn’t found this molecular mechanism but, a cross talk between the VE-cadherin dependent PECAM regulation and adherents molecule to extracellular matrix is possible.
In the end, we characterized a new role of VE-cadherin. This adherent molecule might be crucial to endothelium biology, especially in the control of important endothelial proteins.

Keywords:
Endothelial cells, VE-cadherin, N-cadherin, angiogenesis, p120 catenin, lipid raft, PECAM

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