Hatfield Isabelle, Harvey Innocence, Yates Erika R, Redd JeAnna R, Reiter Lawrence T, Bridges Dave
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163 [2] Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163.
Sci Rep. 2015 Apr 13;5:9676. doi: 10.1038/srep09676.
Myogenesis is an important process during both development and muscle repair. Previous studies suggest that mTORC1 plays a role in the formation of mature muscle from immature muscle precursor cells. Here we show that gene expression for several myogenic transcription factors including Myf5, Myog and Mef2c but not MyoD and myosin heavy chain isoforms decrease when C2C12 cells are treated with rapamycin, supporting a role for mTORC1 pathway during muscle development. To investigate the possibility that mTORC1 can regulate muscle in vivo we ablated the essential dTORC1 subunit Raptor in Drosophila melanogaster and found that muscle-specific knockdown of Raptor causes flies to be too weak to emerge from their pupal cases during eclosion. Using a series of GAL4 drivers we also show that muscle-specific Raptor knockdown also causes shortened lifespan, even when eclosure is unaffected. Together these results highlight an important role for TORC1 in muscle development, integrity and function in both Drosophila and mammalian cells.
成肌作用是发育和肌肉修复过程中的一个重要过程。先前的研究表明，mTORC1在未成熟的肌肉前体细胞形成成熟肌肉的过程中发挥作用。在此我们表明，当用雷帕霉素处理C2C12细胞时，包括Myf5、Myog和Mef2c在内的几种成肌转录因子的基因表达会下降，但MyoD和肌球蛋白重链亚型的基因表达不会下降，这支持了mTORC1通路在肌肉发育过程中的作用。为了研究mTORC1在体内调节肌肉的可能性，我们在黑腹果蝇中敲除了必需的dTORC1亚基Raptor，发现肌肉特异性敲低Raptor会导致果蝇在羽化时过于虚弱而无法从蛹壳中羽化出来。使用一系列GAL4驱动子，我们还表明，即使羽化不受影响，肌肉特异性敲低Raptor也会导致寿命缩短。这些结果共同突出了TORC1在果蝇和哺乳动物细胞的肌肉发育、完整性和功能中的重要作用。
