PMID- 20008564
OWN - NLM
STAT- MEDLINE
DCOM- 20100115
LR  - 20220309
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 187
IP  - 6
DP  - 2009 Dec 14
TI  - Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to 
      severe myopathy.
PG  - 859-74
LID - 10.1083/jcb.200903131 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a key regulator of cell growth that 
      associates with raptor and rictor to form the mTOR complex 1 (mTORC1) and mTORC2, 
      respectively. Raptor is required for oxidative muscle integrity, whereas rictor 
      is dispensable. In this study, we show that muscle-specific inactivation of mTOR 
      leads to severe myopathy, resulting in premature death. mTOR-deficient muscles 
      display metabolic changes similar to those observed in muscles lacking raptor, 
      including impaired oxidative metabolism, altered mitochondrial regulation, and 
      glycogen accumulation associated with protein kinase B/Akt hyperactivation. In 
      addition, mTOR-deficient muscles exhibit increased basal glucose uptake, whereas 
      whole body glucose homeostasis is essentially maintained. Importantly, loss of 
      mTOR exacerbates the myopathic features in both slow oxidative and fast 
      glycolytic muscles. Moreover, mTOR but not raptor and rictor deficiency leads to 
      reduced muscle dystrophin content. We provide evidence that mTOR controls 
      dystrophin transcription in a cell-autonomous, rapamycin-resistant, and 
      kinase-independent manner. Collectively, our results demonstrate that mTOR acts 
      mainly via mTORC1, whereas regulation of dystrophin is raptor and rictor 
      independent.
FAU - Risson, Valerie
AU  - Risson V
AD  - Laboratoire de Biologie Moleculaire de la Cellule, Centre National de la 
      Recherche Scientifique, Unite Mixte de Recherche 5239, IFR128, Universite de 
      Lyon, Equipe Differenciation Neuromusculaire, Ecole Normale Superieure, 69364 
      Lyon Cedex 07, France.
FAU - Mazelin, Laetitia
AU  - Mazelin L
FAU - Roceri, Mila
AU  - Roceri M
FAU - Sanchez, Herve
AU  - Sanchez H
FAU - Moncollin, Vincent
AU  - Moncollin V
FAU - Corneloup, Claudine
AU  - Corneloup C
FAU - Richard-Bulteau, Helene
AU  - Richard-Bulteau H
FAU - Vignaud, Alban
AU  - Vignaud A
FAU - Baas, Dominique
AU  - Baas D
FAU - Defour, Aurelia
AU  - Defour A
FAU - Freyssenet, Damien
AU  - Freyssenet D
FAU - Tanti, Jean-Francois
AU  - Tanti JF
FAU - Le-Marchand-Brustel, Yannick
AU  - Le-Marchand-Brustel Y
FAU - Ferrier, Bernard
AU  - Ferrier B
FAU - Conjard-Duplany, Agnes
AU  - Conjard-Duplany A
FAU - Romanino, Klaas
AU  - Romanino K
FAU - Bauche, Stephanie
AU  - Bauche S
FAU - Hantai, Daniel
AU  - Hantai D
FAU - Mueller, Matthias
AU  - Mueller M
FAU - Kozma, Sara C
AU  - Kozma SC
FAU - Thomas, George
AU  - Thomas G
FAU - Ruegg, Markus A
AU  - Ruegg MA
FAU - Ferry, Arnaud
AU  - Ferry A
FAU - Pende, Mario
AU  - Pende M
FAU - Bigard, Xavier
AU  - Bigard X
FAU - Koulmann, Nathalie
AU  - Koulmann N
FAU - Schaeffer, Laurent
AU  - Schaeffer L
FAU - Gangloff, Yann-Gael
AU  - Gangloff YG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Dystrophin)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, mouse)
RN  - 0 (Utrophin)
RN  - 0 (rictor protein, mouse)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Age Factors
MH  - Animals
MH  - Carrier Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Cells, Cultured
MH  - Dystrophin/genetics/*metabolism
MH  - Electroporation
MH  - Energy Metabolism
MH  - Enzyme Activation
MH  - Female
MH  - Glucose/metabolism
MH  - Glycogen/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria, Muscle/enzymology
MH  - Muscle Contraction
MH  - Muscle, Skeletal/drug effects/*enzymology/physiopathology
MH  - Muscular Dystrophy, Animal/*enzymology/genetics/physiopathology
MH  - Mutation
MH  - Oxidation-Reduction
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & 
      inhibitors/*deficiency/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Rats
MH  - Regulatory-Associated Protein of mTOR
MH  - Severity of Illness Index
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transduction, Genetic
MH  - Utrophin/metabolism
PMC - PMC2806319
EDAT- 2009/12/17 06:00
MHDA- 2010/01/16 06:00
PMCR- 2010/06/14
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/01/16 06:00 [medline]
PHST- 2010/06/14 00:00 [pmc-release]
AID - jcb.200903131 [pii]
AID - 200903131 [pii]
AID - 10.1083/jcb.200903131 [doi]
PST - ppublish
SO  - J Cell Biol. 2009 Dec 14;187(6):859-74. doi: 10.1083/jcb.200903131.