Integrin-Dependent Regulation of Small GTPases: Role in Cell Migration

Abstract

Integrins play a vital role in regulating cell adhesion that drives cell attachment, spreading, and migration. They do so by recruiting and activating several downstream signaling pathways that control actin cytoskeleton remodelling, endocytic and exocytic trafficking, and membrane organization in cells. The spatial and temporal nature of this regulation supports the polarization, leading edge protrusion and trailing edge retraction vital for cell migration. By virtue of their dynamic but tightly controlled regulation, small GTPases activated by integrins constitute vital mediators in this pathway. Their activation in cells is driven by the differential recruitment of GEFs and GAPs. This review looks at the integrin-dependent activation, regulation, and role of the Rho family small GTPases Rac-1, RhoA, and Cdc42 along with the emerging contribution that Ral and Arf6 are making to this pathway. It also discusses the extensive crosstalk between these GTPases at the lamellipodial edge in a migrating cell.