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Mol Cell Biol, March 1998, p. 1580-1589, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Rho Family G Proteins Play a Critical Role in Muscle Differentiation

Hiroyuki Takano,dagger Issei Komuro,* Toru Oka, Ichiro Shiojima, Yukio Hiroi, Takehiko Mizuno, and Yoshio Yazaki

Department of Medicine III, University of Tokyo School of Medicine, Tokyo, Japan

Received 19 May 1997/Returned for modification 3 August 1997/Accepted 26 November 1997

The Rho family GTP-binding proteins play a critical role in a variety of cytoskeleton-dependent cell functions. In this study, we examined the role of Rho family G proteins in muscle differentiation. Dominant negative forms of Rho family proteins and RhoGDI, a GDP dissociation inhibitor, suppressed transcription of muscle-specific genes, while mutationally activated forms of Rho family proteins strongly activated their transcription. C2C12 cells overexpressing RhoGDI (C2C12RhoGDI cells) did not differentiate into myotubes, and expression levels of myogenin, MRF4, and contractile protein genes but not MyoD and myf5 genes were markedly reduced in C2C12RhoGDI cells. The promoter activity of the myogenin gene was suppressed by dominant negative mutants of Rho family proteins and was reduced in C2C12RhoGDI cells. Expression of myocyte enhancer binding factor 2 (MEF2), which has been reported to be required for the expression of the myogenin gene, was reduced at the mRNA and protein levels in C2C12RhoGDI cells. These results suggest that the Rho family proteins play a critical role in muscle differentiation, possibly by regulating the expression of the myogenin and MEF2 genes.

* Corresponding author. Mailing address: Molecular Cardiology Division, Department of Medicine III, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Phone: 81-33815-5411. Fax: 81-33815-2087. E-mail: komuro-tky{at}umin.u-tokyo.ac.jp.

dagger Present address: Department of Medicine III, Chiba University School of Medicine, Chiba, Japan.




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