Nature Cell Biology7, 286 - 294 (2005)
Published online: 20 February 2005; | doi:10.1038/ncb1231
Atrophy of S6K1-/- skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
Mickaël Ohanna1, Andrew K. Sobering1, Thomas Lapointe1, Lazaro Lorenzo1, Christophe Praud1, Emmanuel Petroulakis2, Nahum Sonenberg2, Paul A. Kelly1, Athanassia Sotiropoulos1
& Mario Pende1
1
Inserm, Avenir, U584, Université Paris 5, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, Paris, F-75730, France.
2
Department of Biochemistry and McGill Cancer Center, McGill University, McIntyre Medical Building, Montreal, Quebec, Canada H3G 1Y6.
The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps of muscle development and growth, but the physiological relevance and the downstream effectors are under investigation1,
2,
3,
4,
5,
6. Here we show that S6 kinase 1 (S6K1), a protein kinase activated by nutrients and insulin-like growth factors (IGFs), is essential for the control of muscle cytoplasmic volume by Akt and mTOR. Deletion of S6K1 does not affect myoblast cell proliferation but reduces myoblast size to the same extent as that observed with mTOR inhibition by rapamycin. In the differentiated state, S6K1-/- myotubes have a normal number of nuclei but are smaller, and their hypertrophic response to IGF1, nutrients and membrane-targeted Akt is blunted. These growth defects reveal that mTOR requires distinct effectors for the control of muscle cell cycle and size, potentially opening new avenues of therapeutic intervention against neoplasia or muscle atrophy.
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