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- Title
Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis.
- Authors
Meacci, Elisabetta; Bini, Francesca; Sassoli, Chiara; Martinesi, Maria; Squecco, Roberta; Chellini, Flaminia; Zecchi-Orlandini, Sandra; Francini, Fabio; Formigli, Lucia
- Abstract
We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel activity with Cx43 expression/function, investigating the involvement of the Ca-sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P. TRPC1-dependent functions were also required for the transient increase of m-calpain activity/expression and the subsequent decrease of PKCα levels. Remarkably, Cx43 expression in S1P-treated myoblasts was reduced by m-calpain-siRNA and enhanced by pharmacological inhibition of classical PKCs, stressing the relevance for calpain/PKCα axis in Cx43 protein remodeling. The contribution of this pathway in myogenesis was also investigated. In conclusion, these findings provide novel mechanisms by which S1P regulates myoblast differentiation and offer interesting therapeutic options to improve skeletal muscle regeneration.
- Subjects
TRP channels; PROTEIN-protein interactions; CELLULAR signal transduction; MYOGENESIS; GENE expression; CALPAIN; GAP junctions (Cell biology); BIOACTIVE compounds
- Publication
Cellular & Molecular Life Sciences, 2010, Vol 67, Issue 24, p4269
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-010-0442-3