MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis.
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.
Dept. of Experimental Therapeutics, Translational Research Center, Kyoto Univ. Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Masashi
M
Tagawa
Tomomi
T
Ueyama
Takehiro
T
Ogata
Naofumi
N
Takehara
Norio
N
Nakajima
Koji
K
Isodono
Satoshi
S
Asada
Tomosaburo
T
Takahashi
Hiroaki
H
Matsubara
Hidemasa
H
Oh
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D052283:Creatine Kinase, MM Form / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012038:Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
C532667:Cavin4 protein, mouse; D005419:Flavonoids; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D052283:Creatine Kinase, MM Form; D009218:Myosins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one