Cytoskeleton/stretch-activated ion channel interaction regulates myogenic differentiation of skeletal myoblasts
Article first published online: 12 FEB 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 211, Issue 2, pages 296–306, May 2007
How to Cite
Formigli, L., Meacci, E., Sassoli, C., Squecco, R., Nosi, D., Chellini, F., Naro, F., Francini, F. and Zecchi-Orlandini, S. (2007), Cytoskeleton/stretch-activated ion channel interaction regulates myogenic differentiation of skeletal myoblasts. J. Cell. Physiol., 211: 296–306. doi: 10.1002/jcp.20936
- Issue published online: 26 FEB 2007
- Article first published online: 12 FEB 2007
- Manuscript Accepted: 5 OCT 2006
- Manuscript Received: 23 MAY 2006
- Italian Ministry for University. Grant Number: PRIN 2003
- University of Florence
- Ente Cassa di Risparmio di Firenze
- Ente Cassa di Risparmio di Pistoia e Pescia
In the present study, we investigated the functional interaction between stress fibers (SFs) and stretch-activated channels (SACs) and its possible role in the regulation of myoblast differentiation induced by switch to differentiation culture in the presence or absence of sphingosine 1-phosphate. It was found that there was a clear temporal correlation between SF formation and SAC activation in differentiating C2C12 myoblasts. Inhibition of actin polymerization with the specific Rho kinase inhibitor Y-27632, significantly decreased SAC sensitivity in these cells, suggesting a role for Rho-dependent actin remodeling in the regulation of the channel opening. The alteration of cytoskeletal/SAC functional correlation had also deleterious effects on myogenic differentiation of C2C12 cells as judged by combined confocal immunofluorescence, biochemical and electrophysiological analyses. Indeed, the treatment with Y-27632 or with DHCB, an actin disrupting agent, inhibited the expression of the myogenic markers (myogenin and sarcomeric proteins) and myoblast-myotube transition. The treatment with the channel blocker, GdCl3, also affected myogenesis in these cells. It impaired, in fact, myoblast phenotypic maturation (i.e., reduced the expression of α-sarcomeric actin and skeletal myosin and the activity of creatine kinase) but did not modify promoter activity and protein expression levels of myogenin. The results of this study, together with being in agreement with the general idea that cytoskeletal remodeling is essential for muscle differentiation, describe a novel pathway whereby the formation of SFs and their contraction, generate a mechanical tension to the plasma membrane, activate SACs and trigger Ca2+-dependent signals, thus influencing the phenotypic maturation of myoblasts. J. Cell. Physiol. 211: 296–306, 2007. © 2007 Wiley-Liss, Inc.