J Cell Sci. 2008 Jul 1;121(Pt 13):2246-55. doi: 10.1242/jcs.032003. Epub 2008 Jun 10.

TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Gervasio, O. L., Whitehead, N. P., Yeung, E. W., Phillips, W. D., Allen, D. G.,
["School of Medical Sciences, Discipline of Physiology (F13), Bosch Institute, The University of Sydney, NSW 2006, Australia."]
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.
PMID: 18544631External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Caveolin-3 Inference Prediction 18544631
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Caveolin-3 Co-immunoprecipitation Mouse skeletal muscle cell 18544631
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Caveolin-3 Co-immunofluorescence staining Mouse skeletal muscle section 18544631
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Caveolin-3 Fluorescence resonance energy transfer Mouse skeletal muscle Human Full-length Mouse Full-length 18544631
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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