Skeletal muscle differentiation is a well-orchestrated process regulated by autocrine, paracrine, and endocrine factors via a regulatory network of signal transduction pathways. In recent years the mammalian target of rapamycin (mTOR) has begun to be recognized as a critical regulator of skeletal muscle differentiation, growth and hypertrophy. Work from our laboratory has contributed to the current understanding of mTOR regulation of myoblast differentiation, and has led to the revelation that mTOR regulates multiple stages of myogenesis by assembling distinct pathways, some of which unexpected and yet to be fully delineated. With a combination of biochemical, molecular, cellular and genetic approaches, and utilizing both in vitro and in vivo systems, we aim to fill a sizable gap in the current knowledge of molecular pathways underlying the regulation of skeletal myogenesis by addressing these three major questions: (1) How are the known components of growth-regulating mTOR pathway involved in myogenesis, and what is the mTOR pathway(s) that regulates the initiation of myoblast differentiation in response to amino acids availability signals? (2) What is the mTOR pathway that specifically regulates the second-stage myocyte fusion critical for myotube/myofiber growth and maturation, and which secreted factors regulate this process? (3) What is mTOR's role in muscle regeneration and what are the mechanisms? Our expertise in biochemical characterization of signal transduction mechanisms, our strong preliminary data, and the unique animal models we have created, put us in an ideal position to tackle those questions. Knowledge gained in these studies will contribute to the molecular understanding of skeletal muscle development, repair, regeneration and hypertrophy.

Public Health Relevance

Skeletal muscle differentiation is a well-orchestrated process regulated by autocrine, paracrine, and endocrine factors via multiple signal transduction pathways. Our proposed studies aim to dissect the molecular mechanisms underlying the regulation of skeletal muscle differentiation and regeneration, with a focus on the mammalian target of rapamycin signaling network. Knowledge gained in these studies will contribute to the molecular understanding of skeletal muscle biology, which may have significant impact on health-related issues such as muscular dystrophy, aging or disease-induced muscle atrophy, muscle regeneration, and exercise- induced muscle hypertrophy.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Muscle and Exercise Physiology Study Section (SMEP)
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Boyce, Amanda T
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University of Illinois Urbana-Champaign
Anatomy/Cell Biology
Schools of Arts and Sciences
United States
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Fang, Yimin; Hill, Cristal M; Darcy, Justin et al. (2018) Effects of rapamycin on growth hormone receptor knockout mice. Proc Natl Acad Sci U S A 115:E1495-E1503
Dutta, Debapriya; Lai, Kuan-Yu; Reyes-Ordoñez, Adriana et al. (2018) Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation. J Lipid Res 59:1433-1445
He, Chang; Zeng, Min; Dutta, Debapriya et al. (2017) LanCL proteins are not Involved in Lanthionine Synthesis in Mammals. Sci Rep 7:40980
Arif, Abul; Terenzi, Fulvia; Potdar, Alka A et al. (2017) EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice. Nature 542:357-361
Waldemer-Streyer, Rachel J; Reyes-Ordoñez, Adriana; Kim, Dongwook et al. (2017) Cxcl14 depletion accelerates skeletal myogenesis by promoting cell cycle withdrawal. NPJ Regen Med 2:
Mahmassani, Ziad S; Son, Kook; Pincu, Yair et al. (2017) ?7?1Integrin regulation of gene transcription in skeletal muscle following an acute bout of eccentric exercise. Am J Physiol Cell Physiol 312:C638-C650
Yoon, Mee-Sup; Son, Kook; Arauz, Edwin et al. (2016) Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling. Cell Rep 16:1510-1517
Yoon, Mee-Sup; Rosenberger, Christina L; Wu, Cong et al. (2015) Rapid mitogenic regulation of the mTORC1 inhibitor, DEPTOR, by phosphatidic acid. Mol Cell 58:549-56
Waldemer-Streyer, R J; Chen, J (2015) Myocyte-derived Tnfsf14 is a survival factor necessary for myoblast differentiation and skeletal muscle regeneration. Cell Death Dis 6:e2026
Jain, Ankur; Arauz, Edwin; Aggarwal, Vasudha et al. (2014) Stoichiometry and assembly of mTOR complexes revealed by single-molecule pulldown. Proc Natl Acad Sci U S A 111:17833-8

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