ArticleNature cell biology2022
A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi.EMBO reports · 2026Article
- Obesity, Bariatric Surgery, and Cancer Risk: Nutritional Perspectives and Long-Term Clinical Implications.Nutrients · 2026Review
- Article
- Local insulin-like growth factor-1 and Akt/mTOR signaling in skeletal muscle of lubabegron-supplemented finishing steers.Journal of animal science · 2026Article
- Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome.Frontiers in oncology · 2026Review
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Branched-chain amino acids in muscle growth: mechanisms, physiological functions, and applications.Journal of animal science and biotechnology · 2025Review
- SFPQ-TFE3 reciprocally regulates mTORC1 and induces lineage plasticity in a mouse model of renal tumorigenesis.Nature communications · 2025Article
- ER-phagy Activation by AMFR Attenuates Cardiac Fibrosis Post-Myocardial Infarction via mTORC1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity.bioRxiv : the preprint server for biology · 2025Article
- Nitrogen limitation causes a seismic shift in redox state and phosphorylation of proteins implicated in carbon flux and lipidome remodeling in Rhodotorula toruloides.Biotechnology for biofuels and bioproducts · 2025Article
- Rag GTPases control lysosomal acidification by regulating v-ATPase assembly in Drosophila.The Journal of biological chemistry · 2025Article
- STAT6 mutations compensate for CREBBP mutations and hyperactivate IL4/STAT6/RRAGD/mTOR signaling in follicular lymphoma.Leukemia · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.Nature cell biology · 2024Article
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- A multiprotein signaling complex sustains AKT and mTOR/S6K activity necessary for the survival of cancer cells undergoing stress.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Amino acid availability controls mTORC1 activity via a heterodimeric Rag GTPase complex that functions as a scaffold at the lysosomal surface, bringing together mTORC1 with its activators and effectors. Mammalian cells express four Rag proteins (RagA-D) that form dimers composed of RagA/B bound to RagC/D. Traditionally, the Rag paralogue pairs (RagA/B and RagC/D) are referred to as functionally redundant, with the four dimer combinations used interchangeably in most studies. Here, by using genetically modified cell lines that express single Rag heterodimers, we uncover a Rag dimer code that determines how amino acids regulate mTORC1. First, RagC/D differentially define the substrate specificity downstream of mTORC1, with RagD promoting phosphorylation of its lysosomal substrates TFEB/TFE3, while both Rags are involved in the phosphorylation of non-lysosomal substrates such as S6K. Mechanistically, RagD recruits mTORC1 more potently to lysosomes through increased affinity to the anchoring LAMTOR complex. Furthermore, RagA/B specify the signalling response to amino acid removal, with RagB-expressing cells maintaining lysosomal and active mTORC1 even upon starvation. Overall, our findings reveal key qualitative differences between Rag paralogues in the regulation of mTORC1, and underscore Rag gene duplication and diversification as a potentially impactful event in mammalian evolution.
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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.