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首页> 外文期刊>Cellular Signalling >Expression of Gα_z in C2C12 cells restrains myogenic differentiation
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Expression of Gα_z in C2C12 cells restrains myogenic differentiation

机译：Gα_z在C2C12细胞中的表达抑制成肌分化

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摘要

The recent identification of Gα_z expression in C2C12 myoblasts and its demonstrated interaction with the transcription factor Eya2 inferred an unanticipated role of Gα_z in muscle development. In the present study, endogenous Gα_z mRNA and protein expressions in C2C12 cells increased upon commencement of myogenesis and peaked at around 4-6days after induction but were undetectable in adult skeletal muscle. Surprisingly, stable expression of recombinant Gα_z in C2C12 myoblasts strongly suppressed myotube formation upon serum deprivation, and the constitutively active mutant Gα_zQL exerted more pronounced effects. Transcriptional activities of reporter genes responsive to early (MyoD, MEF2 and myogenin) and late (muscle creatine kinase and myosin heavy chain) myogenic markers were reduced by transiently expressed Gα_zQL. Membrane attachment of Gα_z was apparently required for the suppressive effects because a fatty acylation-deficient Gαz mutant could not inhibit myogenin expression. Introduction of siRNA against Gαz enhanced myogenin-driven luciferase activity and increased myosin heavy chain expression. Immunostaining of C2C12 cells over-expressing Gαz showed delayed nuclear expression of myogenin and severe myotube deformation. Gαz expression was accompanied by reduced levels of Rock2, RhoA and RhoGAP, enhanced expression of Rnd3, and a reduction of serum-responsive factor-driven reporter activity. These results support a novel role of Gα_z in restraining myogenic differentiation through the disruption of Rho signaling.
机译：C2C12成肌细胞中Gα_z表达的最新鉴定及其与转录因子Eya2的相互作用表明，Gα_z在肌肉发育中具有意想不到的作用。在本研究中，C2C12细胞中的内源性Gα_zmRNA和蛋白质表达在成肌开始时增加，并在诱导后约4-6天达到峰值，但在成年骨骼肌中未检测到。令人惊讶地，重组Gα_z在C2C12成肌细胞中的稳定表达强烈抑制了血清剥夺后肌管的形成，并且组成型活性突变体Gα_zQL发挥了更明显的作用。瞬时表达的Gα_zQL降低了对早期（MyoD，MEF2和肌生成素）和晚期（肌肉肌酸激酶和肌球蛋白重链）成肌标记物有响应的报告基因的转录活性。 Gα_z的膜附着显然是抑制作用所必需的，因为缺乏脂肪酰化的Gαz突变体不能抑制肌生成素的表达。针对Gαz的siRNA的引入增强了肌原蛋白驱动的荧光素酶活性，并增加了肌球蛋白的重链表达。过度表达Gαz的C2C12细胞的免疫染色显示，肌原蛋白的核表达延迟，肌管严重变形。 Gαz表达伴随Rock2，RhoA和RhoGAP水平降低，Rnd3表达增强以及血清反应因子驱动的报道分子活性降低。这些结果支持了Gα_z通过破坏Rho信号转导来抑制肌原性分化的新作用。

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