The role of TORC1 in muscle development in Drosophila.

Isabelle Hatfield,Innocence Harvey,Jeanna R Redd,Lawrence T Reiter,Erika R Yates,Dave Bridges

doi:10.1038/srep09676

Isabelle Hatfield, Innocence Harvey + Show 4 more

Open Access

https://doi.org/10.1038/srep09676

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Abstract

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.

Highlights

Myogenesis is an important process during both development and muscle repair
To determine the order in which myogenic markers are induced during myogenesis, we performed a time course experiment in C2C12 cells
MTORC1 is the primary target of rapamycin, studies using rapamycin-insensitive analogs of Mammalian target of rapamycin (mTOR) have suggested there may

Summary

Introduction

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. Using a series of GAL4 drivers we show that muscle-specific Raptor knockdown 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. This kinase responds to nutrient and growth hormone signals in the environment and subsequently phosphorylates targets involved in aging, growth, protein lipid and glycogen metabolism[3,4,5] In addition to these effects on differentiated cells, there is an emerging role for mTORC1 in the regulation of cellular differentiation during development including neurogenesis[6,7], adipogenesis[8] and myogenesis[9,10,11]. In this study we present data supporting an essential developmental role of TORC1 in muscle development and/or integreity

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