TRPC1 regulates skeletal myoblast migration and differentiation.

Details

Serval ID
serval:BIB_DB611CFE2E1A
Type
Article: article from journal or magazin.
Collection
Publications
Title
TRPC1 regulates skeletal myoblast migration and differentiation.
Journal
Journal of cell science
Author(s)
Louis M., Zanou N. (co-first), Van Schoor M., Gailly P.
ISSN
0021-9533 (Print)
ISSN-L
0021-9533
Publication state
Published
Issued date
01/12/2008
Peer-reviewed
Oui
Volume
121
Number
Pt 23
Pages
3951-3959
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Myoblast migration is a key step in myogenesis and regeneration. It allows myoblast alignment and their fusion into myotubes. The process has been shown to involve m-calpain or mu-calpain, two Ca(2+)-dependent cysteine proteases. Here we measure calpain activity in cultured cells and show a peak of activity at the beginning of the differentiation process. We also observed a concomitant and transient increase of the influx of Ca(2+) and expression of TRPC1 protein. Calpains are specifically activated by a store-operated entry of Ca(2+) in adult skeletal muscle fibres. We therefore repressed the expression of TRPC1 in myoblasts and studied the effects on Ca(2+) fluxes and on differentiation. TRPC1-depleted myoblasts presented a largely reduced store-operated entry of Ca(2+) and a significantly diminished transient influx of Ca(2+) at the beginning of differentiation. The concomitant peak of calpain activity was abolished. TRPC1-knockdown myoblasts also accumulated myristoylated alanine-rich C-kinase substrate (MARCKS), an actin-binding protein and substrate of calpain. Their fusion into myotubes was significantly slowed down as a result of the reduced speed of cell migration. Accordingly, migration of control myoblasts was inhibited by 2-5 microM GsMTx4 toxin, an inhibitor of TRP channels or by 50 microM Z-Leu-Leu, an inhibitor of calpain. By contrast, stimulation of control myoblasts with IGF-1 increased the basal influx of Ca(2+), activated calpain and accelerated migration. These effects were not observed in TRPC1-knockdown cells. We therefore suggest that entry of Ca(2+) through TRPC1 channels induces a transient activation of calpain and subsequent proteolysis of MARCKS, which allows in turn, myoblast migration and fusion.
Keywords
Animals, Calcium/metabolism, Calpain/metabolism, Cell Differentiation/physiology, Cell Line, Cell Movement/physiology, Cytosol/metabolism, Insulin-Like Growth Factor I/metabolism, Intracellular Signaling Peptides and Proteins/metabolism, Membrane Proteins/metabolism, Mice, Myoblasts, Skeletal/cytology, Myoblasts, Skeletal/metabolism, Myristoylated Alanine-Rich C Kinase Substrate, TRPC Cation Channels/antagonists & inhibitors, TRPC Cation Channels/metabolism, Transfection
Pubmed
Web of science
Create date
27/01/2023 18:17
Last modification date
14/02/2024 9:36
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