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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2051.)
© 2000 American Heart Association, Inc.

Vascular Biology

Vasodilator-Stimulated Phosphoprotein Is Involved in Stress-Fiber and Membrane Ruffle Formation in Endothelial Cells

Caroline J. Price; Nicholas P. J. Brindle

From the Cardiovascular Research Institute and Department of Surgery, University of Leicester, Leicester, UK.

Correspondence to Dr Nicholas P.J. Brindle, Cardiovascular Research Institute and Department of Surgery, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX UK. E-mail npjb1{at}leicester.ac.uk

Abstract—Vasodilator-stimulated phosphoprotein (VASP) is highly expressed in vascular endothelial cells, where it has been implicated in cellular reorganization 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 endothelial cells to determine in what aspects of cytoskeletal behavior this protein participates. Expression of wild-type VASP induces marked membrane ruffling and formation of prominent stress fibers in bovine aortic endothelial cells. Deletion of the proline-rich domain of VASP abolishes its ability to bind profilin but does not affect ruffling or stress fiber formation. Further deletions reveal a sequence within the carboxy-terminal domain that is responsible for in vivo bundle formation. Ruffling occurs only on the expression of forms of VASP that possess bundling activity and the capacity to bind zyxin/vinculin-derived peptide. The ability of distinct subdomains within VASP to bind adhesion proteins and induce F-actin bundling in vivo suggests that this protein could function in the aggregation and tethering of actin filaments during the formation of endothelial cell–substrate and cell-cell contacts. These data provide a mechanism whereby VASP can influence endothelial migration and organization during capillary formation and modulate vascular permeability via effects on endothelial cell contractility.

Key Words: endothelium • vasodilator-stimulated phosphoprotein • actin • angiogenesis • vasodilators

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