Nouvelle architecture de la jonction adhérente endothéliale

Abstract : Tumoral cells as leucocytes get through the vascular endothelium across adherens junctions, mainly composed of VE-cadherin. This transmigration process disturbs transiently the junctions, impairing so the endothelium integrity.
To understand the mechanisms leading to the opening of adherens junctions, we first determined the proteic composition of the VE-cadherin-based complex of primary endothelial cell (HUVEC) mature adherens junctions. To do so, we developed a method coupling immunoprecipitation and mass spectrometry-based proteomic analysis (LC-nanoESI-MS/MS). Partners of VE-cadherin, so far unknown such as annexin 2 and moesin, were so identified.
Our results demonstrated that, in confluent HUVECs, the VE-cadherin-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the plasma membrane as cell reach confluence. Annexin 2, located in cholesterol rafts, binds both to the actin cytoskeleton and the VE-cadherin-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cadherin-based complex thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by siRNA induces a delocalization of VE-cadherin from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data suggest that the decoupling of the annexin 2/p11 complex from the VE-cadherin-based junction, triggered by Vascular Endothelial Growth Factor facilitates the switch from a quiescent to an immature state.
Moesin seems to interact with the VE-cadherin-based complex in immature junctions of sub-confluent HUVECs. Moesin might be involved in production of early cell-cell contact rather than in adherens junction maturation.
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Submitted on : Tuesday, October 16, 2007 - 11:42:23 AM
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Stéphanie Heyraud. Nouvelle architecture de la jonction adhérente endothéliale. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00179647⟩

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