ArticleG3 (Bethesda, Md.)2016
The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster.
Article in G3 (Bethesda, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.Nature communications · 2025Article
- Review
- NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells.Cell division · 2024Article
- The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.Molecular cell · 2024Article
- Differential amino acid transporter expression in adultmicroPublication biology · 2024Article
- Ancient genomic linkage couples metabolism with erythroid development.bioRxiv : the preprint server for biology · 2023Article
- Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy.Science China. Life sciences · 2023Article
- Functional unknomics: Systematic screening of conserved genes of unknown function.PLoS biology · 2023Article
- Wdr59 promotes or inhibits TORC1 activity depending on cellular context.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Article
- Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.Journal of experimental & clinical cancer research : CR · 2022Review
- SEA and GATOR 10 Years Later.Cells · 2021Review
- FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.Cell death & disease · 2021Article
- Royal jelly attenuates metabolic defects in aBiology open · 2020Article
- Article
- Article
- Review
- Tumor suppressor NPRL2 induces ROS production and DNA damage response.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability. Consistent with increased TORC1 activity, GATOR1 mutants exhibit a cell autonomous increase in cell growth. Notably, escaper nprl2 and nprl3 mutant adults have a profound locomotion defect. In line with a nonautonomous role in the regulation of systemic metabolism, expressing the Nprl3 protein in the fat body, a nutrient storage organ, and hemocytes but not muscles and neurons rescues the motility of nprl3 mutants. Finally, we show that nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation and are extremely sensitive to both amino acid and complete starvation. Thus, in Drosophila, in addition to maintaining baseline levels of TORC1 activity, the GATOR1 complex has retained a critical role in the response to nutrient stress. In summary, the TORC1 inhibitor GATOR1 contributes to multiple aspects of the development and physiology of Drosophila.
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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.