Tagawa Masashi, Ueyama Tomomi, Ogata Takehiro, Takehara Naofumi, Nakajima Norio, Isodono Koji, Asada Satoshi, Takahashi Tomosaburo, Matsubara Hiroaki, Oh Hidemasa
Dept. of Experimental Therapeutics, Translational Research Center, Kyoto Univ. Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Am J Physiol Cell Physiol. 2008 Aug;295(2):C490-8. doi: 10.1152/ajpcell.00188.2008. Epub 2008 May 28.
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.
骨骼肌生成是一个多步骤过程，在此过程中，多核成熟肌纤维由未分化的单核成肌细胞形成。然而，骨骼肌生成的分子机制尚未完全阐明。在此，我们鉴定出肌肉特异性卷曲螺旋蛋白（MURC）是肌生成的正向调节因子。在骨骼肌中，MURC定位于细胞质，并在肌节的Z盘处积累。在C2C12成肌细胞中，MURC的表达与肌细胞生成素的表达同时出现，并在分化为肌管的过程中先于肌节肌球蛋白的表达。RNA干扰（RNAi）介导的MURC敲低损害了C2C12成肌细胞的分化，这伴随着肌细胞生成素表达和ERK激活受损。在C2C12成肌细胞中过表达MURC导致分化促进，在分化过程中肌细胞生成素表达增强且ERK激活。在损伤诱导的肌肉再生过程中，MURC表达增加，与成熟肌纤维相比，在未成熟肌纤维中观察到更高丰度的MURC。此外，ERK在再生组织中被激活，并且在表达MURC的未成熟肌纤维中检测到ERK激活。这些发现表明，MURC通过调节肌细胞生成素表达和ERK激活参与骨骼肌生成。MURC可能在骨骼肌生成分化的分子机制中起关键作用。
