Rho家族G蛋白在肌肉分化中起关键作用。
The Rho family G proteins play a critical role in muscle differentiation.
作者信息
Takano H, Komuro I, Oka T, Shiojima I, Hiroi Y, Mizuno T, Yazaki Y
机构信息
Department of Medicine III, University of Tokyo School of Medicine, Japan.
出版信息
Mol Cell Biol. 1998 Mar;18(3):1580-9. doi: 10.1128/MCB.18.3.1580.
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.
Rho家族GTP结合蛋白在多种依赖细胞骨架的细胞功能中发挥关键作用。在本研究中，我们检测了Rho家族G蛋白在肌肉分化中的作用。Rho家族蛋白和GDP解离抑制剂RhoGDI的显性负性形式抑制了肌肉特异性基因的转录，而Rho家族蛋白的突变激活形式则强烈激活了它们的转录。过表达RhoGDI的C2C12细胞（C2C12RhoGDI细胞）不能分化为肌管，并且C2C12RhoGDI细胞中肌细胞生成素、MRF4和收缩蛋白基因的表达水平显著降低，但MyoD和myf5基因的表达水平未降低。肌细胞生成素基因的启动子活性被Rho家族蛋白的显性负性突变体抑制，并且在C2C12RhoGDI细胞中降低。据报道，肌细胞增强子结合因子2（MEF2）是肌细胞生成素基因表达所必需的，其在C2C12RhoGDI细胞中的mRNA和蛋白质水平均降低。这些结果表明，Rho家族蛋白可能通过调节肌细胞生成素和MEF2基因的表达，在肌肉分化中发挥关键作用。
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