MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis

Abstract

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.

Mechanoprotection by skeletal muscle caveolae

“…Release of cavins from caveolae may play a role in regulating vital cellular processes such as muscle hypertrophy. 30 In conclusion, as well as providing a reservoir of membrane that can flatten into the sarcolemma, we suggest that a number of features of the caveolar system may be important in the protection of the muscle surface. Naturally, numerous questions remain.…”

Caveolae and cancer: A new mechanical perspective

“…[46] Cavin4 was shown to influence cardiac function by activating RhoA and extracellular-signal-regulated kinase (ERK) pathway. [47] Cavin4 is likely to be an interesting candidate for the muscle-related caveolinopathies. Indeed, Cavin4 mutations have recently been linked to human cardiopathies.…”

Molecular mechanisms of clathrin-independent endocytosis

“…There are four homologs of PTRF in mammals (see www.treefam.org, accession TF331031), and two of them [serum deprivation-response protein (SDPR) and SDPRrelated gene product that binds to C-kinase (SRBC)] are also present in caveolae and are important for the recruitment of protein-kinase-C isoforms to these structures (Gustincich and Schneider, 1993;Gustincich et al, 1999;Mineo et al, 1998). The fourth homolog, muscle-restricted coiled-coil protein (MURC), is expressed only in muscle and has a similar subcellular distribution to caveolin 3, the muscle-specific isoform of caveolin Tagawa et al, 2008). It seems probable, then, that all four homologs associate with caveolae and caveolins, and participate in their function.…”