Bonet-Kerrache Armelle, Fortier Mathieu, Comunale Franck, Gauthier-Rouvière Cécile
CRBM (Centre de Recherches en Biochimie Macromoléculaire), CNRS FRE2593, 1919 Route de Mende, 34293 Montpellier Cedex, France.
Biochem J. 2005 Oct 15;391(Pt 2):261-8. doi: 10.1042/BJ20050024.
The Rho family of small GTPases are signalling molecules involved in cytoskeleton remodelling and gene transcription. Their activities are important for many cellular processes, including myogenesis. In particular, RhoA positively regulates skeletal-muscle differentiation. We report in the present study that the active form of RhoA increases the expression of utrophin, the autosomal homologue of dystrophin in the mouse C2C12 and rat L8 myoblastic cell lines. Even though this RhoA-dependent utrophin increase is higher in proliferating myoblasts, it is maintained during myogenic differentiation. This occurs via two mechanisms: (i) transcriptional activation of the utrophin promoter A and (ii) post-translational stabilization of utrophin. In addition, RhoA increases plasma-membrane localization of utrophin. Thus RhoA activation up-regulates utrophin levels and enhances its localization at the plasma membrane.
小GTP酶的Rho家族是参与细胞骨架重塑和基因转录的信号分子。它们的活性对许多细胞过程都很重要,包括肌生成。特别是,RhoA正向调节骨骼肌分化。我们在本研究中报告,RhoA的活性形式增加了抗肌萎缩蛋白在小鼠C2C12和大鼠L8成肌细胞系中的常染色体同源物——抗肌萎缩蛋白相关蛋白的表达。尽管这种RhoA依赖性的抗肌萎缩蛋白相关蛋白增加在增殖的成肌细胞中更高,但在肌源性分化过程中仍保持。这通过两种机制发生:(i)抗肌萎缩蛋白相关蛋白启动子A的转录激活和(ii)抗肌萎缩蛋白相关蛋白的翻译后稳定。此外,RhoA增加了抗肌萎缩蛋白相关蛋白在质膜的定位。因此,RhoA激活上调了抗肌萎缩蛋白相关蛋白水平,并增强了其在质膜的定位。