Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling.
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.
Palazzo
Alexander F
AF
Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.
Eng
Christina H
CH
Schlaepfer
David D
DD
Marcantonio
Eugene E
EE
Gundersen
Gregg G
GG
D000107:Acetylation; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000080865:Formins; D005677:G(M1) Ganglioside / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D005353:Fibronectins; D000080865:Formins; D017261:Glycosylphosphatidylinositols; D016023:Integrins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D005677:G(M1) Ganglioside; D002784:Cholesterol; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein