| First Author | Gervásio OL | Year | 2008 |
| Journal | J Cell Sci | Volume | 121 |
| Issue | Pt 13 | Pages | 2246-55 |
| PubMed ID | 18544631 | Mgi Jnum | J:139759 |
| Mgi Id | MGI:3810022 | Doi | 10.1242/jcs.032003 |
| Citation | Gervasio OL, et al. (2008) TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy. J Cell Sci 121(Pt 13):2246-55 |
| abstractText | Transient receptor potential canonical 1 (TRPC1), a widely expressed calcium (Ca(2+))-permeable channel, is potentially involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Ca(2+) 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 Ca(2+) 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 Ca(2+) 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. |
