MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis.
MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis.
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DOI：
10.1152/ajpcell.00188.2008
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发表时间：
2008-08
期刊：
影响因子：
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通讯作者：
M. Tagawa;T. Ueyama;T. Ogata;N. Takehara;Norio Nakajima;K. Isodono;S. Asada;Tomosaburo Takahashi;H. Matsubara;H. Oh
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文献类型：
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作者：
M. Tagawa;T. Ueyama;T. Ogata;N. Takehara;Norio Nakajima;K. Isodono;S. Asada;Tomosaburo Takahashi;H. Matsubara;H. Oh
骨骼肌发生是一个多步骤的过程，通过这个过程，由未分化的单核成肌细胞形成多核成熟肌纤维。然而，骨骼肌发生的分子机制尚未完全阐明。在这里，我们发现肌肉限制性螺旋线圈(MURC)蛋白是肌肉发生的正调节因子。在骨骼肌中，MURC定位于细胞质，并聚集在肌节的Z盘处。在C2C12成肌细胞中，在分化为肌管的过程中，MURC的表达与肌生成素的表达一致，并且先于肌节肌球蛋白的表达。RNA干扰(RNAi)介导的MURC基因敲除导致C2C12成肌细胞分化受损，并伴随着肌生成素表达和ERK活性的降低。在C2C12成肌细胞中过表达MURC可促进分化，促进分化过程中肌生成素的表达和ERK的激活。在损伤诱导的肌肉再生过程中，MURC的表达增加，并且在未成熟的肌纤维中观察到比成熟的肌纤维更丰富的MURC。此外，ERK在再生组织中被激活，在表达MURC的未成熟肌纤维中检测到ERK激活。这些发现表明，MURC参与了骨骼肌的发生，而骨骼肌的发生是通过调节肌生成素的表达和ERK的激活来实现的。MURC可能在骨骼肌源性分化的分子机制中发挥关键作用。
Skeletal myogenesis is a multistep process by which multinucleated mature muscle fibers are formed from undifferentiated, mononucleated myoblasts. However, the molecular mechanisms of skeletal myogenesis have not been fully elucidated. Here, we identified muscle-restricted coiled-coil (MURC) protein as a positive regulator of myogenesis. In skeletal muscle, MURC was localized to the cytoplasm with accumulation in the Z-disc of the sarcomere. In C2C12 myoblasts, MURC expression occurred coincidentally with myogenin expression and preceded sarcomeric myosin expression during differentiation into myotubes. RNA interference (RNAi)-mediated knockdown of MURC impaired differentiation in C2C12 myoblasts, which was accompanied by impaired myogenin expression and ERK activation. Overexpression of MURC in C2C12 myoblasts resulted in the promotion of differentiation with enhanced myogenin expression and ERK activation during differentiation. During injury-induced muscle regeneration, MURC expression increased, and a higher abundance of MURC was observed in immature myofibers compared with mature myofibers. In addition, ERK was activated in regenerating tissue, and ERK activation was detected in MURC-expressing immature myofibers. These findings suggest that MURC is involved in the skeletal myogenesis that results from modulation of myogenin expression and ERK activation. MURC may play pivotal roles in the molecular mechanisms of skeletal myogenic differentiation.