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Localized Stabilization of Microtubules by Integrin- and FAK-Facilitated Rho Signaling
Alexander F. Palazzo,1
Christina H. Eng,1,2
David D. Schlaepfer,4
Eugene E. Marcantonio,1,3
Gregg G. Gundersen1,3*
Abstract:
Microtubule (MT) stabilization is regulated by the small guanosinetriphosphate (GTP)binding protein Rho and its effector,mammalian homolog of Diaphanous (mDia), in migrating cells,but factors responsible for localized stabilization at the leadingedge are unknown. We report that integrin-mediated activationof focal adhesion kinase (FAK) at the leading edge is requiredfor MT stabilization by the Rho-mDia signaling pathway in mousefibroblasts. MT stabilization also involved FAK-regulated localizationof a lipid raft marker, ganglioside GM1, to the leading edge.The integrin-FAK signaling pathway may facilitate Rho-mDia signalingthrough GM1, or through a specialized membrane domain containingGM1, to stabilize MTs in the leading edge of migrating cells.
1 Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA. 2 Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, New York, NY 10032, USA. 3 Department of Pathology, Columbia University, New York, NY 10032, USA. 4 Department of Immunology, Scripps Research Institute, La Jolla, CA 92307, USA.
* To whom correspondence should be addressed. E-mail: ggg1{at}columbia.edu
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