ArticleNature2017
KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers.
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Who cites it
211 citing papers in PubMed, 312 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- The Legionella pneumophila effector SidL is an adenylyltransferase that modifies the glycolytic intermediate 3-phosphoglycerate.Molecular cell · 2026Article
- Review
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- Article
- Host genetic regulation of rumen 6-hydroxymelatonin reduces methane emissions in dairy cattle.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- METTL1-mediated mOncogene · 2026Article
- Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis.Nature cell biology · 2026Article
- The Clinical Spectrum and Neurodevelopmental Pathogenesis of KPTN-Related Disorder in a Mouse Model.Annals of neurology · 2026Article
- Structure and function of the yeast amino acid-sensing SEAC-EGOC supercomplex.Nature structural & molecular biology · 2026Article
- Brain organoid models of SZT2-related disease reveal an overproduction of outer radial glial cells through mTORC1 activation.Scientific reports · 2026Article
- Activation of mitochondrial CPS1 promotes dormant ovarian follicle activation via arginine elevation and the mTORC1 pathway.Frontiers in cell and developmental biology · 2026Article
- 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
- Caught in the act: how a brake on cell growth is anchored to lysosomes.Nature structural & molecular biology · 2025Article
- Architecture of the human KICSTOR and GATOR1-KICSTOR complexes.Nature structural & molecular biology · 2025Article
- Multilayered regulation of TORC1 signaling by Ait1, Gcn2, and SEAC/GATOR during nitrogen limitation and starvation.Nature communications · 2025Article
- Signs of immune dysregulation in second-trimester maternal blood RNA profiles in late-onset preeclampsia.Scientific reports · 2025Article
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
151 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth that responds to diverse environmental signals and is deregulated in many human diseases, including cancer and epilepsy. Amino acids are a key input to this system, and act through the Rag GTPases to promote the translocation of mTORC1 to the lysosomal surface, its site of activation. Multiple protein complexes regulate the Rag GTPases in response to amino acids, including GATOR1, a GTPase activating protein for RAGA, and GATOR2, a positive regulator of unknown molecular function. Here we identify a protein complex (KICSTOR) that is composed of four proteins, KPTN, ITFG2, C12orf66 and SZT2, and that is required for amino acid or glucose deprivation to inhibit mTORC1 in cultured human cells. In mice that lack SZT2, mTORC1 signalling is increased in several tissues, including in neurons in the brain. KICSTOR localizes to lysosomes; binds and recruits GATOR1, but not GATOR2, to the lysosomal surface; and is necessary for the interaction of GATOR1 with its substrates, the Rag GTPases, and with GATOR2. Notably, several KICSTOR components are mutated in neurological diseases associated with mutations that lead to hyperactive mTORC1 signalling. Thus, KICSTOR is a lysosome-associated negative regulator of mTORC1 signalling, which, like GATOR1, is mutated in human disease.
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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.