Localized Stabilization of Microtubules by Integrin- and FAK-Facilitated Rho Signaling

Abstract

Microtubule (MT) stabilization is regulated by the small guanosine triphosphate (GTP)–binding protein Rho and its effector, mammalian homolog of Diaphanous (mDia), in migrating cells, but factors responsible for localized stabilization at the leading edge are unknown. We report that integrin-mediated activation of focal adhesion kinase (FAK) at the leading edge is required for MT stabilization by the Rho-mDia signaling pathway in mouse fibroblasts. MT stabilization also involved FAK-regulated localization of a lipid raft marker, ganglioside G_M1, to the leading edge. The integrin-FAK signaling pathway may facilitate Rho-mDia signaling through G_M1, or through a specialized membrane domain containing G_M1, to stabilize MTs in the leading edge of migrating cells.