Caveolin 3 is associated with the calcium release complex and is modified via in vivo triadin modification.
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.
Vassilopoulos
Stéphane
S
INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France.
Oddoux
Sarah
S
Groh
Séverine
S
Cacheux
Marine
M
Fauré
Julien
J
Brocard
Julie
J
Campbell
Kevin P
KP
Marty
Isabelle
I
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D051244:Caveolin 3 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D002352:Carrier Proteins; C495548:Cav3 protein, mouse; D051244:Caveolin 3; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C498270:Trdn protein, mouse; D002118:Calcium