TRPC1 binds to caveolin-3 and is regulated by Src kinase - Role in Duchenne muscular dystrophy

Othon L. Gervásio, Nicholas R. Whitehead, Wai Ella Yeung, William D. Phillips, David G. Allen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

122 Citations (Scopus)

Abstract

Transient receptor potential canonical 1 (TRPC1), a widely expressed calcium (Ca2+)-permeable channel, is potentially involved in the pathogenesis of Duchenne muscular dystrophy (DMD). C22+ influx through stretch-activated channels, possibly formed by TRPC1, induces muscle-cell damage in the mdx mouse, an animal model of DMD. In this study, we showed that TRPC1, caveolin-3 and Src-kinase protein levels are increased in mdx muscle compared with wild type. TRPC1 and caveolin-3 colocalised and co-immunoprecipitated. Direct binding of TRPC1-CFP to caveolin-3-YFP was confirmed in C2 myoblasts by fluorescence energy resonance transfer (FRET). Caveolin-3-YFP targeted TRPC1-CFP to the plasma membrane. Hydrogen peroxide, a reactive oxygen species (ROS), increased Src activity and enhanced Ca2+ influx, but only in C2 myoblasts co-expressing TRPC1 and caveolin-3. In mdx muscle, Tiron, a ROS scavenger, and PP2, a Src inhibitor, reduced stretch-induced Ca2+ entry and increased force recovery. Because ROS production is increased in mdx/DMD, these results suggest that a ROS-Src-TRPC1/caveolin-3 pathway contributes to the pathogenesis of mdx/DMD.
Original languageEnglish
Pages (from-to)2246-2255
Number of pages10
JournalJournal of Cell Science
Volume121
Issue number13
DOIs
Publication statusPublished - 1 Jul 2008

Keywords

  • Caveolin-3
  • Duchenne muscular dystrophy
  • mdx
  • Src
  • TRPC1

ASJC Scopus subject areas

  • Cell Biology

Cite this