RhoA GTPase is dispensable for actomyosin regulation but is essential for mitosis in primary Mouse embryonic fibroblasts

Jaime Melendez, Kristy Stengel, Xuan Zhou, Bharesh K. Chauhan, Marcella Debidda, Paul Andreassen, Richard A. Lang, Yi Zheng

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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 p21Cip1 or p27Kip1. 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.

Original languageEnglish (US)
Pages (from-to)15132-15137
Number of pages6
JournalJournal of Biological Chemistry
Volume286
Issue number17
DOIs
StatePublished - Apr 29 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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