Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation–contraction coupling supramolecular complex
Copyright policy )Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation–contraction coupling supramolecular complex
The protein mammalian target of rapamycin (mTOR) is a serine/threonine kinase regulating a number of biochemical pathways controlling cell growth. mTOR exists in two complexes termed mTORC1 and mTORC2. Regulatory associated protein of mTOR (raptor) is associated with mTORC1 and is essential for its function. Ablation of raptor in skeletal muscle results in several phenotypic changes including decreased life expectancy, increased glycogen deposits and alterations of the twitch kinetics of slow fibres. In the present paper, we show that in muscle-specific raptor knockout (RamKO), the bulk of glycogen phosphorylase (GP) is mainly associated in its cAMP-non-stimulated form with sarcoplasmic reticulum (SR) membranes. In addition, 3[H]–ryanodine and 3[H]–PN200-110 equilibrium binding show a ryanodine to dihydropyridine receptors (DHPRs) ratio of 0.79 and 1.35 for wild-type (WT) and raptor KO skeletal muscle membranes respectively. Peak amplitude and time to peak of the global calcium transients evoked by supramaximal field stimulation were not different between WT and raptor KO. However, the increase in the voltage sensor-uncoupled RyRs leads to an increase of both frequency and mass of elementary calcium release events (ECRE) induced by hyper-osmotic shock in flexor digitorum brevis (FDB) fibres from raptor KO. The present study shows that the protein composition and function of the molecular machinery involved in skeletal muscle excitation–contraction (E–C) coupling is affected by mTORC1 signalling.
- University of Ferrara Italy
- Wake Forest University United States
- University Hospital of Basel Switzerland
- Instituto Venezolano de Investigaciones Científicas Venezuela
- University of Basel Switzerland
Male, Mice, Knockout, Calcium Channels, L-Type, Ryanodine, Glycogen Phosphorylase, Ryanodine Receptor Calcium Release Channel, Regulatory-Associated Protein of mTOR, Mechanistic Target of Rapamycin Complex 1, Mice, Sarcoplasmic Reticulum, Gene Expression Regulation, Isometric Contraction, Multiprotein Complexes, Animals, Calcium, Muscle, Skeletal, Evoked Potentials, Excitation Contraction Coupling, Adaptor Proteins, Signal Transducing, Signal Transduction
Male, Mice, Knockout, Calcium Channels, L-Type, Ryanodine, Glycogen Phosphorylase, Ryanodine Receptor Calcium Release Channel, Regulatory-Associated Protein of mTOR, Mechanistic Target of Rapamycin Complex 1, Mice, Sarcoplasmic Reticulum, Gene Expression Regulation, Isometric Contraction, Multiprotein Complexes, Animals, Calcium, Muscle, Skeletal, Evoked Potentials, Excitation Contraction Coupling, Adaptor Proteins, Signal Transducing, Signal Transduction
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