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Regulation of ensothelial barrier properties through activation of Rho family GTPases

Final Activity Report Summary - ENDO ADHESION (Regulation of ensothelial barrier properties through activation of Rho family GTPases)

The present study aims to elucidate signalling mechanisms residing at the cell-cell junctions of endothelial cells and especially at the adherens junctions. Adherens structures depend on transmembrane molecules called cadherins. Cadherins are cell-cell adhesion receptors that interact in homophilic fashion to connect cells of the same type. Adherens junction proteins include the armadillo repeat proteins b-catenin and p120 and actin associated proteins a-catenin, a-actinin and vinculin and others.

We studied the properties of adherens junctions molecules using endothelial cells as a model system, because of the dynamic character of their junctions. Endothelial barrier function is dependent on VE-cadherin, an endothelial specific cadherin. Regulation of endothelial barrier function is an important property of the endothelium required for migration of salutes and cells from blood to tissues.

Cadherin proteins are involved in serious diseases like atherosclerosis, inflammation and thrombosis. We examine the role of VE-cadherin in signalling and participation of actin rearrangement during cell-cell disruption mediated by the actin remodelling protein Cdc42. We also investigate the topology of VE-cadherin in the plasma membrane and we come to conclusion that its topology at the plasma membrane depends on a specialized lipid microenvironment that includes the Phosphatidyl-Inositol-phosphate (PIP2).