ArticleThe Journal of physiology2013
Eccentric contractions increase the phosphorylation of tuberous sclerosis complex-2 (TSC2) and alter the targeting of TSC2 and the mechanistic target of rapamycin to the lysosome.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- Piezo1 channels enhance anabolic signaling activation induced by electrical stimulation of cultured myotubes.FEBS open bio · 2025Article
- Comparative analysis of acute eccentric contraction-induced changes to the skeletal muscle transcriptome in young and aged mice and humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.Experimental physiology · 2024Article
- The Plateau in Muscle Growth with Resistance Training: An Exploration of Possible Mechanisms.Sports medicine (Auckland, N.Z.) · 2024Review
- Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.Physiological reviews · 2023Review
- The duration of glucocorticoid treatment alters the anabolic response to high-force muscle contractions.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism.Sports medicine and health science · 2023Review
- Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle.Amino acids · 2023Article
- Alcohol, Resistance Exercise, and mTOR Pathway Signaling: An Evidence-Based Narrative Review.Biomolecules · 2022Review
- Resistance exercise enhances long-term mTORC1 sensitivity to leucine.Molecular metabolism · 2022Article
- Strength Training in Swimming.International journal of environmental research and public health · 2022Review
- Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle.Frontiers in cell and developmental biology · 2021Review
- Skeletal Muscle Recovery from Disuse Atrophy: Protein Turnover Signaling and Strategies for Accelerating Muscle Regrowth.International journal of molecular sciences · 2020Review
- More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle.American journal of physiology. Cell physiology · 2020Review
- Hallmarks of frailty and osteosarcopenia in prematurely aged PolgAJournal of cachexia, sarcopenia and muscle · 2020Article
- Leucine-enriched amino acids maintain peripheral mTOR-Rheb localization independent of myofibrillar protein synthesis and mTORC1 signaling postexercise.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- mTOR at the nexus of nutrition, growth, ageing and disease.Nature reviews. Molecular cell biology · 2020Review
- PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase.Nature communications · 2020Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
The goal of this study was to determine whether the mechanical activation of mechanistic target of rapamycin (mTOR) signalling is associated with changes in phosphorylation of tuberous sclerosis complex-2 (TSC2) and targeting of mTOR and TSC2 to the lysosome. As a source of mechanical stimulation, mouse skeletal muscles were subjected to eccentric contractions (ECs). The results demonstrated that ECs induced hyper-phosphorylation of TSC2 and at least part of this increase occurred on residue(s) that fall within RxRxxS/T consensus motif(s). Furthermore, in control muscles, we found that both mTOR and TSC2 are highly enriched at the lysosome. Intriguingly, ECs enhanced the lysosomal association of mTOR and almost completely abolished the lysosomal association of TSC2. Based on these results, we developed a new model that could potentially explain how mechanical stimuli activate mTOR signalling. Furthermore, this is the first study to reveal that the activation of mTOR is associated with the translocation of TSC2 away from the lysosome. Since a large number of signalling pathways rely on TSC2 to control mTOR signalling, our results have potentially revealed a fundamental mechanism via which not only mechanical, but also various other types of stimuli, control mTOR signalling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.