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.
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."]
["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: 18544631
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPC1 |
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Caveolin-3 | Inference | Prediction | 18544631 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
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| Validation: In vivo validation
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|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
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Caveolin-3 | Co-immunoprecipitation | Mouse skeletal muscle cell | 18544631 | |||||
| TRPC1 |
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Caveolin-3 | Co-immunofluorescence staining | Mouse skeletal muscle section | 18544631 | |||||
| TRPC1 |
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Caveolin-3 | Fluorescence resonance energy transfer | Mouse skeletal muscle | Human | Full-length | Mouse | Full-length | 18544631 | |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)