TY - JOUR
T1 - Atrophy of S6K1-/- skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
AU - Ohanna, Mickaël
AU - Sobering, Andrew K.
AU - Lapointe, Thomas
AU - Lorenzo, Lazaro
AU - Praud, Christophe
AU - Petroulakis, Emmanuel
AU - Sonenberg, Nahum
AU - Kelly, Paul A.
AU - Sotiropoulos, Athanassia
AU - Pende, Mario
PY - 2005/3
Y1 - 2005/3
N2 - 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 investigation. 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.
AB - 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 investigation. 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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U2 - 10.1038/ncb1231
DO - 10.1038/ncb1231
M3 - Article
C2 - 15723049
AN - SCOPUS:20044392290
SN - 1465-7392
VL - 7
SP - 286
EP - 294
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 3
ER -