Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1.
In migrating fibroblasts, RhoA and its effector mDia1 regulate the selective stabilization of microtubules (MTs) polarized in the direction of migration. The conserved formin homology 2 domain of mDia1 is involved both in actin polymerization and MT stabilization, and the relationship between these two activities is unknown. We found that latrunculin A (LatA) and jasplakinolide, actin drugs that release mDia1 from actin filament barbed ends, stimulated stable MT formation in serum-starved fibroblasts and caused a redistribution of mDia1 onto MTs. Knockdown of mDia1 by small interfering RNA (siRNA) prevented stable MT induction by LatA, whereas blocking upstream Rho or integrin signaling had no effect. In search of physiological regulators of mDia1, we found that actin-capping protein induced stable MTs in an mDia1-dependent manner and inhibited the translocation of mDia on the ends of growing actin filaments. Knockdown of capping protein by siRNA reduced stable MT levels in proliferating cells and in starved cells stimulated with lysophosphatidic acid. These results show that actin-capping protein is a novel regulator of MT stability that functions by antagonizing mDia1 activity toward actin filaments and suggest a novel form of actin-MT cross-talk in which a single factor acts sequentially on actin and MTs.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Francesca
F
Bartolini
Nagendran
N
Ramalingam
Gregg G
GG
Gundersen
D051344:Actin Capping Proteins / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D000080865:Formins; D005799:Genes, Dominant; D018698:Glutamic Acid / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D041681:NIH 3T3 Cells; D015398:Signal Transduction / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D051344:Actin Capping Proteins; D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D047630:Depsipeptides; C491464:Diap1 protein, mouse; C405804:EB1 microtubule binding proteins; D000080865:Formins; D016023:Integrins; D008869:Microtubule-Associated Proteins; D053778:Thiazolidines; C057531:jasplakinolide; D018698:Glutamic Acid; D014443:Tyrosine; D020741:rho GTP-Binding Proteins; C037067:latrunculin A