ArticleMolecular and cellular biology2015
Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 1 of them a synthesis that pooled it.
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Who cites it
184 citing papers in PubMed, 1 synthesis or guideline pooled it, 252 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Regulation of Amino Acid Transporters and Sensors in Response to a High protein Diet: A Randomized Controlled Trial in Elderly Men.The journal of nutrition, health & aging · 2019Trial
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- pH-mediated activation of the lysosomal arginine sensor SLC38A9.FEBS letters · 2026Article
- SLC38A9 Regulation Affects Hippocampal Neuronal Autophagy: A Potential Alzheimer's Therapeutic Approach by Suppressing Alzheimer's Disease-Related Protein Deposition.CNS neuroscience & therapeutics · 2026Article
- Critical Roles and Molecular Mechanisms of Chaperone-Mediated Autophagy in Infections.International journal of molecular sciences · 2026Review
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- pH-dependent regulation in SLC38A9.bioRxiv : the preprint server for biology · 2025Article
- ORP5 promotes cardiac hypertrophy by regulating the activation of mTORC1 on lysosome.Journal of advanced research · 2025Article
- mTORC1 senses glutamine and other amino acids through GCN2.The EMBO journal · 2025Article
- SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes.Life science alliance · 2025Article
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Animal amino acid sensor - A review.Animal bioscience · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Review
- Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases.Nature reviews. Molecular cell biology · 2024Review
- Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
124 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues, such as nutrient status and energy level. Amino acids induce mTORC1 activation on lysosomes via the small Rag GTPases and the Ragulator complex, thereby controlling protein translation and cell growth. Here, we identify the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex. SLC38A9 localizes with Rag-Ragulator complex components on lysosomes and associates with Rag GTPases in an amino acid-sensitive and nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1 activity in the presence of amino acids and in response to amino acid replenishment following starvation. Conversely, SLC38A9 overexpression causes RHEB (Ras homolog enriched in brain) GTPase-dependent hyperactivation of mTORC1 and partly sustains mTORC1 activity upon amino acid deprivation. Intriguingly, during amino acid starvation mTOR is retained at the lysosome upon SLC38A9 depletion but fails to be activated. Together, the findings of our study reveal SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to mTORC1 activity.
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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.