The Rho family G proteins play a critical role in muscle differentiation.
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.
Takano
H
H
Department of Medicine III, University of Tokyo School of Medicine, Japan.
Komuro
I
I
Oka
T
T
Shiojima
I
I
Hiroi
Y
Y
Mizuno
T
T
Yazaki
Y
Y
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis; D018008:Myogenin / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020742:rhoA GTP-Binding Protein
C569638:ARHGDIA protein, human; D000199:Actins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D064326:MEF2 Transcription Factors; C503799:MYOG protein, human; C503801:Myog protein, mouse; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D014157:Transcription Factors; C063403:myogenic factor 6; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D019204:GTP-Binding Proteins; D018995:Myosin Heavy Chains; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein