| Autor: |
You JS; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., McNally RM; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Jacobs BL; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Privett RE; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Gundermann DM; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Lin KH; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Steinert ND; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Goodman CA; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Institute of Health and Sport, Victoria University, Melbourne, Victoria, Australia.; Australian Institute for Musculoskeletal Science, Victoria University, St. Albans, Victoria, Australia., Hornberger TA; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA. |
| Abstrakt: |
It is well known that an increase in mechanical loading can induce skeletal muscle hypertrophy, and a long standing model in the field indicates that mechanical loads induce hypertrophy via a mechanism that requires signaling through the mechanistic target of rapamycin complex 1 (mTORC1). Specifically, it has been widely proposed that mechanical loads activate signaling through mTORC1 and that this, in turn, promotes an increase in the rate of protein synthesis and the subsequent hypertrophic response. However, this model is based on a number of important assumptions that have not been rigorously tested. In this study, we created skeletal muscle specific and inducible raptor knockout mice to eliminate signaling by mTORC1, and with these mice we were able to directly demonstrate that mechanical stimuli can activate signaling by mTORC1, and that mTORC1 is necessary for mechanical load-induced hypertrophy. Surprisingly, however, we also obtained multiple lines of evidence that indicate that mTORC1 is not required for a mechanical load-induced increase in the rate of protein synthesis. This observation highlights an important shortcoming in our understanding of how mechanical loads induce hypertrophy and illustrates that additional mTORC1-independent mechanisms play a critical role in this process.-You, J.-S., McNally, R. M., Jacobs, B. L., Privett, R. E., Gundermann, D. M., Lin, K.-H., Steinert, N. D., Goodman, C. A., Hornberger, T. A. The role of raptor in the mechanical load-induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy. |
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