Research Article

Cellular and Molecular Life Sciences

, Volume 67, Issue 24, pp 4269-4285

First online:

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

  • Elisabetta MeacciAffiliated withDepartment of Biochemical Sciences, University of FlorenceInteruniversity Institute of Myology (IIM)
  • , Francesca BiniAffiliated withDepartment of Biochemical Sciences, University of FlorenceInteruniversity Institute of Myology (IIM)
  • , Chiara SassoliAffiliated withDepartment of Anatomy, Histology, and Forensic Medicine, University of FlorenceInteruniversity Institute of Myology (IIM)
  • , Maria MartinesiAffiliated withDepartment of Biochemical Sciences, University of Florence
  • , Roberta SqueccoAffiliated withDepartment of Physiological Sciences, University of FlorenceInteruniversity Institute of Myology (IIM)
  • , Flaminia ChelliniAffiliated withDepartment of Anatomy, Histology, and Forensic Medicine, University of Florence
  • , Sandra Zecchi-OrlandiniAffiliated withDepartment of Anatomy, Histology, and Forensic Medicine, University of FlorenceInteruniversity Institute of Myology (IIM)
  • , Fabio FranciniAffiliated withDepartment of Physiological Sciences, University of FlorenceInteruniversity Institute of Myology (IIM)
  • , Lucia FormigliAffiliated withDepartment of Anatomy, Histology, and Forensic Medicine, University of FlorenceInteruniversity Institute of Myology (IIM) Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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 Ca2+-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.

Keywords

Stretch-activated channels Gap junctions Myogenesis Bioactive lipids Calpain