RhoA signaling via serum response factor plays an obligatory role in myogenic differentiation

Lei Wei, Wei Zhou, Jeffrey D. Croissant, Finn Erik Johansen, Ron Prywes, Ashok Balasubramanyam, Robert J. Schwartz

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Serum response factor (SRF) plays a central role during myogenesis, being required for the expression of striated α-actin genes. As shown here, the small GTPase RhoA-dependent activation of SRF results in the expression of muscle-specific genes, thereby promoting myogenic differentiation in myoblast cell lines. Co-expression of activated V14-RhoA and SRF results in an approximately 10-fold activation of the skeletal α-actin promoter in replicating myoblasts, while SRFpm1, a dominant negative SRF mutant, blocks RhoA dependent skeletal α-actin promoter activity. Serum withdrawal further potentiates RhoA- and SRF-mediated activation of α-actin promoter to about 30-fold in differentiated myotubes. In addition, the proximal SRE1 in the skeletal α-actin promoter is sufficient to mediate RhoA signaling via SRF. Furthermore, SRFpm1 and to a lesser extent dominant negative N19-RhoA inhibit myoblast fusion, postreplicative myogenic differentiation, and expression of direct SRF targets such as skeletal α-actin and indirect targets such as myogenin and α-myosin heavy chain. Moreover, RhoA also stimulates the autoregulatable murine SRF gene promoter in myoblasts, and the expression level of SRF is reduced in myoblasts overexpressing N19-RhoA. Our study supports the concept that RhoA signaling via SRF serves as an obligatory muscle differentiation regulatory pathway.

Original languageEnglish (US)
Pages (from-to)30287-30294
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number46
DOIs
StatePublished - Nov 13 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Wei, L., Zhou, W., Croissant, J. D., Johansen, F. E., Prywes, R., Balasubramanyam, A., & Schwartz, R. J. (1998). RhoA signaling via serum response factor plays an obligatory role in myogenic differentiation. Journal of Biological Chemistry, 273(46), 30287-30294. https://doi.org/10.1074/jbc.273.46.30287