The control of endothelial cell functions by adherens junctions.

Cell to cell junctions are important regulators of endothelial responses both in quiescent and angiogenic vessels. Endothelial cells express tight and adherens junctional structures. Although different in their specific molecular composition, these junctional complexes present a relatively similar general arrangement. Both types of junctions are formed by transmembrane adhesive proteins that bind homophilically to identical proteins on an adjacent cell and start a sequence of signalling events. Signal transmission is mediated by interaction with cytoplasmic and transmembrane partners. Adherens junctions are ubiquitous along the vascular tree. In these structures adhesion is mediated by VE-cadherin and its intracellular partners. In vitro and in vivo data show that VE-cadherin is required for endothelial integrity in quiescent vessels and for the correct organization of new vessels. VE-cadherin regulates endothelial functions through different mechanisms that include: (i) direct activation of signalling molecules such as PI3 kinase and Rac, to sustain survival and organization of the actin cytoskeleton; (ii) regulation of gene transcription, possibly modulating the nuclear level of transcription co-factors such as beta-catenin and p120; (iii) formation of complexes with growth factor receptors, such as the type 2 receptor of VEGF (VEGFR2) and modulation of their signalling properties.