Regulates myoblast migration and TRPC1 differentiation.
(2008) Belgian Society of Physiology — Location: UCL woluwé, Belgium (11.November.2008)
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- Abstract
- Myoblasts migration is a key step in myogenesis and regeneration. It allows myoblasts alignment and fusion into myotubes. This process has been shown to involve m- or μ- calpains, two calcium-dependent cysteine proteases. In the present paper, we measured calpain activity in situ (fluorometric measurements) and show, for the first time, a peak of activity at the beginning of the differentiation process. We also observed a concomitant and transient increase of the influx of Ca2+ and of the expression of TRPC1 protein. Besides, we recently reported that, in adult skeletal muscle fibres, calpains were specifically activated by a store-operated entry of calcium. In the present study, we therefore repressed the expression of TRPC1 in myoblasts and studied its influence on Ca2+ fluxes and on differentiation. TRPC1 knocked down myoblasts presented a largely reduced store-operated entry of calcium and a significantly diminished transient influx of calcium at the beginning of differentiation. The concomitant peak of calpain activity was abolished. TRPC1 knocked down myoblasts also presented an accumulation of myristoylated alanine-rich C-kinase substrate (MARCKS), an actin-binding protein, substrate of calpain. Finally, their fusion into myotubes was significantly slowed down, due to a reduced speed of cell migration. Accordingly, migration of control myoblasts was inhibited by 2 to 5 μM GsMTx4 toxin, an inhibitor of TRPC1 or by 50 μM Z-Leu-Leu, an inhibitor of calpain. In contrast, stimulation of control myoblasts with IGF-1 increased the basal influx of Ca2+, activated calpain and accelerated migration. These effects were not observed in TRPC1 knocked down cells. We therefore suggest that an entry of calcium through TRPC1 channels induces a transient activation of calpain, a subsequent proteolysis of MARCKS, allowing in its turn, myoblasts migration and fusion.
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Zanou, N., Louis, M., Van Schoor, M., & Gailly, P. (2008). Regulates myoblast migration and TRPC1 differentiation. Belgian Society of Physiology, UCL woluwé, Belgium. https://hdl.handle.net/2078.5/224988