| Abstract | Caveolins are membrane scaffolding proteins that associate with and regulate a variety of signalling proteins, including ion channels. A deficiency in caveolin-3 (Cav-3), the major striated muscle isoform, is responsible for skeletal muscle disorders, such as limb-girdle muscular dystrophy 1C (LGMD 1C). The molecular mechanisms leading to the muscle wasting that characterizes this pathology are poorly understood. Here we show that a loss of Cav-3 induced by the expression of the LGMD 1C-associated mutant P104L (Cav-3(P104L)) provokes a reduction by half of the maximal conductance of the voltage-dependent L-type Ca(2+) channel in mouse primary cultured myotubes and fetal skeletal muscle fibres. Confocal immunomiscrocopy indicated a colocalization of Cav-3 and Ca(v)1.1, the pore-forming subunit of the L-type Ca(2+) channel, at the surface membrane and in the developing T-tubule network in control myotubes and fetal fibres. In myotubes expressing Cav-3(P104L), the loss of Cav-3 was accompanied by a 66% reduction in Ca(v)1.1 mean labelling intensity. Our results suggest that Cav-3 is involved in L-type Ca(2+) channel membrane function and localization in skeletal muscle cells and that an alteration of L-type Ca(2+) channels could be involved in the physiopathological mechanisms of caveolinopathies. |
| Authors | Harold Couchoux, Bruno Allard, Claude Legrand, Vincent Jacquemond, Christine Berthier
(Affiliation: University Lyon 1, CNRS, Laboratory of Integrative, Cellular and Molecular Physiology, Villeurbanne, F-69622, France.)
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| Journal | The Journal of physiology
(J Physiol)
Vol. 580
Issue Pt.3
Pg. 745-54
(May 1 2007)
ISSN: 0022-3751 England |
| PMID | 17317753
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Calcium Channels, L-Type
- Caveolin 3
- Proline
- Leucine
|
| Topics |
- Animals
- Calcium Channels, L-Type
(metabolism)
- Caveolin 3
(deficiency, genetics, metabolism)
- Cells, Cultured
- Electric Conductivity
- Embryo, Mammalian
- Leucine
- Mice
- Muscle Cells
(metabolism)
- Muscle Fibers, Skeletal
(metabolism)
- Muscle, Skeletal
(metabolism)
- Muscular Dystrophies
(genetics)
- Mutation
- Proline
- Tissue Distribution
|
