Vasodilator-stimulated phosphoprotein: crucial for activation of Rac1 in endothelial barrier maintenance.

摘要

The endothelium provides a selective barrier separating blood vessels and the interstitial tissue.1 The intercellular cleft is sealed by tight junctions and mechanical cohesion is provided by adherens junctions. Additionally, integrin-mediated anchoring of endothelial cells to the extracellular matrix contributes to endothelial barrier functions. All of these junctions are composed of transmembrane proteins that are linked directly or indirectly to the actin cytoskele-ton via adaptor proteins. Therefore, it is conceivable that actin dynamics modulate junctional integrity and endothelial barrier functions in vivo. Because GTPases of the Rho family regulate cell adhesion and cytoskeletal reorganization, they are important regulators of the endothelial barrier. In particular, Rac1 is well known to be required for maintenance of endothelial barrier functions. Recently, the actin-binding vasodilator-stimulated phosphoprotein (VASP) has been recognized to act in concert with Rac1 in endothelial barrier regulation. Here, we will discuss the current knowledge on the mechanisms underlying VASP-dependent endothelial barrier regulation.