The molecular organization of endothelial junctions and their functional role in vascular morphogenesis and permeability

We review here our work on the molecular and functional organization of end othelial cell-to-cell junctions. The first part of the review is dedicated to VE-cadherin, characterized by our group few years ago. This protein is a member of the large family of transmembrane adhesion proteins called cadhe rins. It is endothelial cell specific and plays a major role in the organiz ation of adherens junctions. Inactivation of VE-cadherin gene or in vivo tr uncation of its cytoplasmic tail leads to a lethal phenotype due to the lac k of correct organization of the vasculature in the embryo. We found that t he defect was due to apoptosis of endothelial cells, which became unrespons ive to the survival signal induced by vascular endothelial cell growth fact or. Our data indicate that VE-cadherin may act as a scaffolding protein abl e to associate vascular endothelial cell growth factor receptor and to prom ote its signaling. In the second part of the review we consider another pro tein more recently discovered by us and called junctional adhesion molecule (JAM). This protein is a small immunoglobulin which is located at tight ju nctions in the endothelium and in epithelial cells. Evidence is discussed i ndicating that JAM takes part in the organization of tight junctions and mo dulates leukocyte extravasation through endothelial intercellular junctions in vitro and in vivo. The general role of tight junctions in endothelial c ells is also discussed.