Vasodilator-stimulated phosphoprotein is involved in stress-fiber and membrane ruffle formation in endothelial cells

Vasodilator-stimulated phosphoprotein (VASP) is highly expressed in vascula r endothelial cells, where it has been implicated in cellular reorganizatio n during angiogenesis, as well as in endothelial retraction and changes in vessel permeability, However, the cellular functions of VASP are not known. In this study, we have expressed wild-type and mutant forms of VASP in end othelial cells to determine in what aspects of cytoskeletal behavior this p rotein participates. Expression of wild-type VASP induces marked membrane r uffling and formation of prominent stress fibers in bovine aortic endotheli al cells. Deletion of the proline-rich domain of VASP abolishes its ability to bind profilin but does not affect ruffling or stress fiber formation. F urther deletions reveal a sequence within the carboxy-terminal domain that is responsible for in vivo bundle formation. Ruffling occurs only on the ex pression of forms of VASP that possess bundling activity and the capacity t o bind zyxin/vinculin-derived peptide. The ability of distinct subdomains w ithin VASP to bind adhesion proteins and induce F-actin bundling in vivo su ggests that this protein could function in the aggregation and tethering of actin filaments during the formation of endothelial cell-substrate and cel l-cell contacts. These data provide a mechanism whereby VASP can influence endothelial migration and organization during capillary formation and modul ate vascular permeability via effects on endothelial cell contractility.