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First published online 10 June 2008
doi: 10.1242/jcs.032003

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

¹ School of Medical Sciences, Discipline of Physiology (F13), Bosch Institute, The University of Sydney, NSW 2006, Australia
² Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

^* Author for correspondence (e-mail: davida{at}physiol.usyd.edu.au)

Accepted 22 April 2008

Transient receptor potential canonical 1 (TRPC1), a widely expressed calcium (Ca²⁺)-permeable channel, is potentially involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Ca²⁺ 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.

Key words: Duchenne muscular dystrophy, Src, TRPC1, Caveolin-3, mdx

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