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Loss of caveolin‐3 induced by the dystrophy‐associated P104L mutation impairs L‐type calcium channel function in mouse skeletal muscle cells
Author(s) -
Couchoux Harold,
Allard Bruno,
Legrand Claude,
Jacquemond Vincent,
Berthier Christine
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.124198
Subject(s) - myogenesis , skeletal muscle , caveolin 3 , microbiology and biotechnology , myocyte , colocalization , biology , chemistry , voltage dependent calcium channel , muscular dystrophy , dystrophy , endocrinology , medicine , calcium , signal transduction , caveolae , genetics
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.