DHPR alpha1S subunit controls skeletal muscle mass and morphogenesis. - Archive ouverte HAL Access content directly
Journal Articles EMBO Journal Year : 2010

DHPR alpha1S subunit controls skeletal muscle mass and morphogenesis.

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Abstract

The alpha1S subunit has a dual function in skeletal muscle: it forms the L-type Ca(2+) channel in T-tubules and is the voltage sensor of excitation-contraction coupling at the level of triads. It has been proposed that L-type Ca(2+) channels might also be voltage-gated sensors linked to transcriptional activity controlling differentiation. By using the U7-exon skipping strategy, we have achieved long-lasting downregulation of alpha1S in adult skeletal muscle. Treated muscles underwent massive atrophy while still displaying significant amounts of alpha1S in the tubular system and being not paralysed. This atrophy implicated the autophagy pathway, which was triggered by neuronal nitric oxide synthase redistribution, activation of FoxO3A, upregulation of autophagy-related genes and autophagosome formation. Subcellular investigations showed that this atrophy was correlated with the disappearance of a minor fraction of alpha1S located throughout the sarcolemma. Our results reveal for the first time that this sarcolemmal fraction could have a role in a signalling pathway determining muscle anabolic or catabolic state and might act as a molecular sensor of muscle activity.
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Dates and versions

inserm-00515849 , version 1 (08-09-2010)

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France Piétri-Rouxel, Christel Gentil, Stéphane Vassilopoulos, Dominique Baas, Etienne Mouisel, et al.. DHPR alpha1S subunit controls skeletal muscle mass and morphogenesis.. EMBO Journal, 2010, 29 (3), pp.643-54. ⟨10.1038/emboj.2009.366⟩. ⟨inserm-00515849⟩
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