Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration

Abstract

Integrin αvβ3 has an important role in the proliferation, survival, invasion and migration of vascular endothelial cells1,2. Like other integrins, αvβ3 can exist in different functional states with respect to ligand binding. These changes involve both affinity modulation, by which conformational changes in the integrin heterodimer govern affinity for individual extracellular matrix proteins, and avidity modulation, by which changes in lateral mobility and integrin clustering affect the binding of cells to multivalent matrices. Here we have used an engineered monoclonal antibody Fab (antigen-binding fragment) named WOW-1, which binds to activated integrins αvβ3 and αvβ5 from several species3, to investigate the role of αvβ3 activation in endothelial cell behaviour. Because WOW-1 is monovalent, it is insensitive to changes in integrin clustering and therefore reports only changes in affinity. WOW-1 contains an RGD tract in its variable region and binds only to unoccupied, high-affinity integrins. By using WOW-1, we have identified the selective recruitment of high-affinity integrins as a mechanism by which lamellipodia promote formation of new adhesions at the leading edge in cell migration.

Cite this article

Kiosses, W., Shattil, S., Pampori, N. et al. Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3, 316–320 (2001). https://doi.org/10.1038/35060120

View full text

>> Full Text:   Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration