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            <funder>This work was supported by grants from Association Française contre les Myopathies (AFM), from Groupement d'Intêret Scientifique (GIS)-Maladies Rares, from Agence Nationale de la Recherche (ANR-Maladies Rares), from Société Française de Myologie (SFM) and from Fondation Ducoin.</funder>
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                <term xml:lang="ro">caveolin-3</term>
                <term xml:lang="ro">ryanodine receptor</term>
                <term xml:lang="ro">calcium release complex</term>
                <term xml:lang="ro">mouse skeletal muscle</term>
                <term xml:lang="ro">adenovirus</term>
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              <p>The triadin isoforms Trisk 95 and Trisk 51 are both components of the skeletal muscle calcium release complex. To investigate the specific role of Trisk 95 and Trisk 51 isoforms in muscle physiology, we overexpressed Trisk 95 or Trisk 51 using adenovirus-mediated gene transfer in skeletal muscle of newborn mice. Overexpression of either Trisk 95 or Trisk 51 alters the muscle fiber morphology, while leaving unchanged the expression of the ryanodine receptor, the dihydropyridine receptor, and calsequestrin. We also observe an aberrant expression of caveolin 3 in both Trisk 95- and Trisk 51-overexpressing skeletal muscles. Using a biochemical approach, we demonstrate that caveolin 3 is associated with the calcium release complex in skeletal muscle. Taking advantage of muscle and non-muscle cell culture models and triadin null mouse skeletal muscle, we further dissect the molecular organization of the caveolin 3-containing calcium release complex. Our data demonstrate that the association of caveolin 3 with the calcium release complex occurs via a direct interaction with the transmembrane domain of the ryanodine receptor. Taken together, these data suggest that caveolin 3-containing membrane domains and the calcium release complex are functionally linked and that Trisk 95 and Trisk 51 are instrumental to the regulation of this interaction, the integrity of which may be crucial for muscle physiology.</p>
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