Journal
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
Volume 14, Issue 1, Pages 83-88Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MCO.0b013e3283406f3e
Keywords
amino acid transporters; mTORC1; protein synthesis
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Funding
- U.S. NIH/National Institute of Arthritis and Musculoskeletal and Skin Disease [R01 AR049877]
- NIH/National Institute on Aging [P30 AG024832]
- NIH/National Center for Research Resources [1UL1RR029876-01]
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR029876] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR049877] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P30AG024832] Funding Source: NIH RePORTER
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Purpose of review To highlight the recent research pertaining to the cellular mechanisms linking amino acid availability, mTORC1 signaling, and muscle protein metabolism. Recent findings Activation of the mTORC1 pathway in response to amino acids may be dependent upon cellular relocalization of mTORC1, a process that appears to involve the Rag GTPases. Recent studies have also identified other intracellular proteins, such as hVps34 and MAP4K3, and specific amino acid transporters as necessary links between amino acid availability and mTORC1. In human skeletal muscle, it appears that mTORC1 activity increases the expression of several amino acid transporters, which may be an important adaptive response to sensitize muscle to a subsequent increase in amino acid availability. Summary The precise cellular mechanisms linking amino acids to mTORC1 signaling and muscle protein metabolism are currently not well understood. More defined cellular mechanisms are beginning to emerge suggesting a role for several intracellular proteins including hVps34, MAP4K3, and Rag GTPases. Additionally, specific amino acid transporters may have a role both upstream and downstream of mTORC1. Continued investigation into the precise cellular mechanisms linking amino acid availability and muscle protein metabolism will help facilitate improvements in existing therapies for conditions of muscle wasting.
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