The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism

Tinline-Goodfellow, Cassidy; Lees, Matthew; Hodson, Nathan

doi:10.1016/j.smhs.2022.11.004

Cited by 6 publications

(4 citation statements)

References 116 publications

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“…This spatial regulation of mTOR is particularly important in skeletal muscle with mTOR co-localising with the lysosome in basal conditions and then translocating to the cell periphery, in close proximity to capillaries, in response to feeding and resistance exercise (210) . One current suggestion is that mTOR trafficking is important for translational control, allowing close proximity with focal adhesion complexes involved with mechanotransduction, with the microvasculature and associated amino acid transporters, and with the ribosomal translational apparatus which is also close to the sarcolemma (211) .…”

Section: Regulatory Mechanisms and Signalling Pathways Involved In Mu...mentioning

confidence: 99%

Post-natal muscle growth and protein turnover: a narrative review of current understanding

Millward

2023

Nutr. Res. Rev.

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A model explaining the dietary-protein driven post-natal skeletal muscle growth and protein turnover in the rat is updated, and the mechanisms involved described in this narrative review. Dietary protein controls both length and muscle growth which are interrelated through mechanotransduction mechanisms with muscle growth induced by both stretching subsequent to bone length growth and from internal work against gravity. This induces satellite cell activation, myogenesis and remodeling of the extracellular matrix, establishing a growth capacity for myofibre length and cross-sectional area. Protein deposition within this capacity is enabled by adequate dietary protein and other key nutrients. After briefly reviewing the experimental animal origins of the growth model, key concepts and processes important for growth are reviewed. These include the growth in number and size of the myonuclear domain, satellite cell activity during post-natal development and the autocrine/paracrine action of IGF-1. Regulatory and signalling pathways reviewed include developmental mechanotransduction; signalling through the insulin/IGF-1-PI3K-Akt and the Ras-MAPK pathways in the myofibre and during mechanotransduction of satellite cells. Likely pathways activated by maximal-intensity muscle contractions are highlighted and the regulation of the capacity for protein synthesis in terms of ribosome assembly and the translational regulation of 5-TOPmRNA classes by mTORC1 and LARP1 are discussed. Evidence for and potential mechanisms by which volume limitation of muscle growth can occur which would limit protein deposition within the myofibre is reviewed. An understanding of how muscle growth is achieved allows better nutritional management of its growth in health and disease.

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Section: Regulatory Mechanisms and Signalling Pathways Involved In Mu...mentioning

confidence: 99%

Post-natal muscle growth and protein turnover: a narrative review of current understanding

Millward

2023

Nutr. Res. Rev.

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“…The kinase activity of mTORC1 and its downstream targets are dynamically regulated by proteinprotein interactions and intracellular translocation and colocalization (for review see Ref. (61) ). Once activated, mTORC1 stimulates MPS by phosphorylating the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and p70 S6 kinase 1 (p70S6K1).…”

Section: Muscle Protein Synthesis In Response To Amino Acids and Exer...mentioning

confidence: 99%

The effects of branched-chain amino acids on muscle protein synthesis, muscle protein breakdown and associated molecular signalling responses in humans: an update

Kaspy,

Hannaian,

Bell

et al. 2023

Nutr. Res. Rev.

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Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are three of the nine indispensable amino acids, and are frequently consumed as a dietary supplement by athletes and recreationally active individuals alike. The popularity of BCAA supplements is largely predicated on the notion that they can stimulate rates of muscle protein synthesis (MPS) and suppress rates of muscle protein breakdown (MPB), the combination of which promotes a net anabolic response in skeletal muscle. To date, several studies have shown that BCAA (particularly leucine) increase the phosphorylation status of key proteins within the mechanistic target of rapamycin (mTOR) signalling pathway involved in the regulation of translation initiation in human muscle. Early research in humans demonstrated that BCAA provision reduced indices of whole-body and MPB; however, there was no stimulatory effect of BCAA on MPS. In contrast, recent work has demonstrated that BCAA intake can stimulate postprandial MPS rates at rest and can further increase MPS rates during recovery after a bout of resistance exercise. The purpose of this evidence-based narrative review is to critically appraise the available research pertaining to studies examining the effects of BCAA on MPS, MPB, and associated molecular signalling responses in humans. Overall, BCAA can activate molecular pathways that regulate translation initiation, reduce indices of whole-body and MPB, and transiently stimulate MPS rates. However, the stimulatory effect of BCAA on MPS rates is less than the response observed following ingestion of a complete protein source providing the full complement of indispensable amino acids.

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“…This special issue highlights comprehensive reviews and researches on topics in fundamentally important areas of skeletal muscle physiology. 1 , 2 , 3 , 4 , 5 , 6 The most important adaptive response of skeletal muscle to exercise, particularly resistant exercise, is increased protein synthesis, which is critical for promoting muscle hypertrophy and/or preventing atrophy. This process plays an essential role in promoting and maintaining skeletal muscle contractile and metabolic functions.…”

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confidence: 99%

“…The review by Tinline-Goodfellow et al. 2 elegantly reviewed the literature on the regulation of muscle protein synthesis with a focus on the mechanistic target of the rapamycin (mTOR) complex 1 (mTORC1) pathway. The authors not only provided a comprehensive review of findings in support of the indispensable role of mTORC1 in promoting muscle protein synthesis in response to growth factors, nutrients and mechanical stimuli, but also brought our attention to the role of skeletal muscle periphery region, including recruitment of mTORC1 to this region, in promoting protein synthesis.…”

mentioning

confidence: 99%