Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation-contraction coupling supramolecular complex

Biochem J. 2015 Feb 15;466(1):123-35. doi: 10.1042/BJ20140935.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / genetics*
  • Calcium Channels, L-Type / metabolism
  • Evoked Potentials / physiology
  • Excitation Contraction Coupling / physiology
  • Gene Expression Regulation
  • Glycogen Phosphorylase / genetics
  • Glycogen Phosphorylase / metabolism
  • Isometric Contraction
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes / genetics*
  • Multiprotein Complexes / metabolism
  • Muscle, Skeletal / metabolism*
  • Regulatory-Associated Protein of mTOR
  • Ryanodine / metabolism
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism


  • Adaptor Proteins, Signal Transducing
  • CACNA1S protein, mouse
  • Calcium Channels, L-Type
  • Multiprotein Complexes
  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Glycogen Phosphorylase
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • Calcium