title: RhoA GTPase is dispensable for actomyosin regulation but is essential for mitosis in primary mouse embryonic fibroblasts.
abstract: RhoA, the founding member of mammalian Rho GTPase family, is thought to be essential for actomyosin regulation. To date, the physiologic function of RhoA in mammalian cell regulation has yet to be determined genetically. Here we have created RhoA conditional knock-out mice. Mouse embryonic fibroblasts deleted of RhoA showed no significant change in actin stress fiber or focal adhesion complex formation in response to serum or LPA, nor any detectable change in Rho-kinase signaling activity. Concomitant knock-out or knockdown of RhoB and RhoC in the RhoA(-/-) cells resulted in a loss of actin stress fiber and focal adhesion similar to that of C3 toxin treatment. Proliferation of RhoA(-/-) cells was impaired due to a complete cell cycle block during mitosis, an effect that is associated with defective cytokinesis and chromosome segregation and can be readily rescued by exogenous expression of RhoA. Furthermore, RhoA deletion did not affect the transcriptional activity of Stat3, NFκB, or serum response factor, nor the expression of the cell division kinase inhibitor p21(Cip)1 or p27(Kip1). These genetic results demonstrate that in primary mouse embryonic fibroblasts, RhoA is uniquely required for cell mitosis but is redundant with related RhoB and RhoC GTPases in actomyosin regulation.
authors: Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, Ohio 45229, USA.
authors: Jaime
authors: J
authors: Melendez
authors: Kristy
authors: K
authors: Stengel
authors: Xuan
authors: X
authors: Zhou
authors: Bharesh K
authors: BK
authors: Chauhan
authors: Marcella
authors: M
authors: Debidda
authors: Paul
authors: P
authors: Andreassen
authors: Richard A
authors: RA
authors: Lang
authors: Yi
authors: Y
authors: Zheng
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology*; D022001:Focal Adhesions; D051379:Mice; D008938:Mitosis; D022502:Stress Fibers; D014158:Transcription, Genetic; D018631:ras Proteins; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein
chemical_list: D000205:Actomyosin; C526380:RhoA protein, mouse; C512911:Rhoc protein, mouse; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein