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 GM1, to the leading edge. The integrin-FAK signaling pathway may facilitate Rho-mDia signaling through GM1, or through a specialized membrane domain containing GM1, to stabilize MTs in the leading edge of migrating cells.