Atrophy of S6K1-/- skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control

被引:307
作者
Ohanna, M
Sobering, AK
Lapointe, T
Lorenzo, L
Praud, C
Petroulakis, E
Sonenberg, N
Kelly, PA
Sotiropoulos, A
Pende, M
机构
[1] Univ Paris 05, INSERM, Avenir,U584, Fac Med Necker Enfants Malad, F-75730 Paris, France
[2] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[3] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada
关键词
D O I
10.1038/ncb1231
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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(1-6). 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.
引用
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页码:286 / 294
页数:9
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