REGULATION OF ENDOTHELIAL-CELL ADHESION BY PROFILIN

Background: Although profilin is believed to be an essential regulator of the actin cytoskeleton in most cells, its precise role in mammalia n cells remains unknown. We have used replication-incompetent adenovir us carrying the human profilin I cDNA as a means rapidly to increase t he concentration of profilin in human aortic endothelial cells 12-31-f old above baseline - levels never before achieved in mammalian cells. Results: The concentration of filamentous actin was not detectably aff ected by profilin overexpression. Actin stress fibers were, however, a bsent from areas of high profilin content in overexpressing cells, and the bulk of filaments was located at the periphery of the cells. We o bserved a gradient in the distribution of overexpressed profilin in mi grating endothelial cells, with most profilin molecules concentrated n ear the advancing edge where focal contacts are being formed and focal adhesion proteins are located. Profilin overexpression resulted in in creased recruitment of fibronectin receptors to the plasma membrane. A dhesion of endothelial cells to fibronectin was markedly and selective ly increased by profilin overexpression, Conclusions: We conclude that an important role for profilin in mammalian cells may be its contribu tion to the formation of focal contacts, particularly those involving the fibronectin receptor.