Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho.
Microtubule depolymerization has multiple consequences that include actin stress fiber and focal adhesion assembly, increased tyrosine phosphorylation and DNA synthesis. Similar effects induced by serum, or agents such as lysophosphatidic acid, have previously been shown to be mediated by the GTP-binding protein Rho. We have investigated whether the effects of microtubule depolymerization are similarly mediated by Rho and show that they are blocked by the specific Rho inhibitor, C3 transferase. Because microtubule depolymerization induces these effects in quiescent cells, in which Rho is largely inactive, we conclude that microtubule depolymerization leads to activation of Rho. The activation of Rho in response to microtubule depolymerization and the consequent stimulation of contractility suggest a mechanism by which microtubules may regulate microfilament function in various motile phenomena. These range from growth cone extension to the development of the contractile ring during cytokinesis, in which there are interactions between the microtubule and microfilament systems.
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599, USA. bliu@med.unc.edu
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D016475:3T3 Cells / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D011108:Polymers; D013314:Stress, Mechanical; D020741:rho GTP-Binding Proteins
D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D011108:Polymers; D004247:DNA; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D015739:Nocodazole