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.