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Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy.

Valérie Risson | Laetitia Mazelin | Mila Roceri | Hervé Sanchez | Vincent Moncollin | Claudine Corneloup | Hélène Richard-Bulteau | Alban Vignaud | Dominique Baas | Aurélia Defour | Damien Freyssenet | Jean-François Tanti | Yannick Le-Marchand-Brustel | Bernard Ferrier | Agnès Conjard-Duplany | Klaas Romanino | Stéphanie Bauché | Daniel Hantaï | Matthias Mueller | Sara C Kozma | George Thomas | Markus A Rüegg | Arnaud Ferry | Mario Pende | Xavier Bigard | Nathalie Koulmann | Laurent Schaeffer | Yann-Gaël Gangloff
The Journal of cell biology | 2009

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.

Pubmed ID: 20008564

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RRID:SCR_002368

Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.

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C2C12 (tool)

RRID:CVCL_0188

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