Atrophy of S6K1-/- skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
Atrophy of S6K1-/- skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
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DOI：
10.1038/ncb1231
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发表时间：
2005-03-01
影响因子：
21.3
通讯作者：
Pende, M
中科院分区：
文献类型：
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作者：
Ohanna, M;Sobering, AK;Pende, M
哺乳动物雷帕霉素靶蛋白（mTOR）和Akt蛋白调节肌肉发育和生长的各个步骤，但生理相关性和下游效应物正在研究中（1-6）。在这里，我们表明，S6激酶1（S6 K1），一种由营养素和胰岛素样生长因子（IGFs）激活的蛋白激酶，是Akt和mTOR控制肌肉细胞质体积所必需的。S6 K1的缺失不影响成肌细胞的增殖，但降低成肌细胞的大小，其程度与雷帕霉素抑制mTOR所观察到的相同。在分化状态下，S6 K1（-/-）肌管具有正常数量的细胞核，但较小，并且它们对IGF 1、营养物质和膜靶向Akt的肥大反应减弱。这些生长缺陷表明，mTOR需要不同的效应子来控制肌肉细胞周期和大小，这可能为肿瘤或肌肉萎缩的治疗干预开辟了新的途径。
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.