You Jae-Sung, Kim Kookjoo, Steinert Nathaniel D, Chen Jie, Hornberger Troy A
Department of Comparative Biosciences in the School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Cell Death Discov. 2021 Apr 12;7(1):74. doi: 10.1038/s41420-021-00460-w.
Skeletal muscle denervation occurs in diverse conditions and causes severe muscle atrophy. Signaling by mammalian target of rapamycin complex 1 (mTORC1) plays a central role in the maintenance of skeletal muscle mass by regulating net protein balance; yet, its role in denervation-induced atrophy is unclear. In this study, by using skeletal muscle-specific and inducible raptor knockout mice, we demonstrate that signaling through mTORC1 is activated during denervation and plays an essential role in mitigating the atrophy of non-type IIB muscle fibers. Measurements of protein synthesis rates of individual fibers suggest that denervation increases protein synthesis specifically in non-type IIB muscle fibers and that mTORC1 is required for this event. Furthermore, denervation induced a more pronounced increase in the level of phosphorylated ribosomal S6 protein in non-type IIB muscle fibers than in type IIB muscle fibers. Collectively, our results unveil a novel role for mTORC1 in mediating a fiber type-specific regulation of muscle size and protein synthesis during denervation.
骨骼肌去神经支配发生于多种情况，并导致严重的肌肉萎缩。雷帕霉素复合物1（mTORC1）的哺乳动物靶点信号传导通过调节净蛋白质平衡在维持骨骼肌质量中起核心作用；然而，其在去神经支配诱导的萎缩中的作用尚不清楚。在本研究中，通过使用骨骼肌特异性和可诱导的猛禽敲除小鼠，我们证明在去神经支配期间通过mTORC1的信号传导被激活，并且在减轻非IIB型肌纤维的萎缩中起重要作用。对单个纤维蛋白质合成速率的测量表明，去神经支配特异性地增加了非IIB型肌纤维中的蛋白质合成，并且该事件需要mTORC1。此外，去神经支配在非IIB型肌纤维中比在IIB型肌纤维中诱导了更明显的磷酸化核糖体S6蛋白水平的增加。总的来说，我们的结果揭示了mTORC1在去神经支配期间介导肌肉大小和蛋白质合成的纤维类型特异性调节中的新作用。
