ArticleNature2017
TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 122 citations in OpenAlex.
- Physiological architecture and evolutionary origins of cellular adaptability.bioRxiv : the preprint server for biology · 2026Article
- Imaging Techniques for the Study of Protein Condensates and Filaments and Their Applications.International journal of molecular sciences · 2026Review
- The A2357T substitution in the kinase domain of yeast Tor1 confers growth promoting TORC1 activity independent of Gtr1/2 and Pib2.Scientific reports · 2026Article
- Expression of Wild-Type and Mutant Human TDP-43 in Yeast Inhibits TOROID (TORC1 Organized in Inhibited Domain) Formation and Autophagy Proportionally to the Levels of TDP-43 Toxicity.International journal of molecular sciences · 2024Article
- The PP2A-like phosphatase Ppg1 mediates assembly of the Far complex to balance gluconeogenic outputs and enables adaptation to glucose depletion.PLoS genetics · 2024Article
- Phosphoregulation of the yeast Pma1 H+-ATPase autoinhibitory domain involves the Ptk1/2 kinases and the Glc7 PP1 phosphatase and is under TORC1 control.PLoS genetics · 2024Article
- The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease.Nature reviews. Molecular cell biology · 2023Review
- Agglomeration: when folded proteins clump together.Biophysical reviews · 2023Review
- EGOC inhibits TOROID polymerization by structurally activating TORC1.Nature structural & molecular biology · 2023Article
- Article
- Ultrastructure expansion microscopy reveals the cellular architecture of budding and fission yeast.Journal of cell science · 2022Article
- Quiescence inAnnual review of genetics · 2022Review
- TDP-43 Toxicity in Yeast Is Associated with a Reduction in Autophagy, and Deletions ofViruses · 2022Article
- TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle.Journal of cell science · 2022Article
- Conserved Pib2 regions have distinct roles in TORC1 regulation at the vacuole.Journal of cell science · 2022Article
- Live cell microscopy: From image to insight.Biophysics reviews · 2022Review
- TORC1 signaling modulates Cdk8-dependent GAL gene expression in Saccharomyces cerevisiae.Genetics · 2021Article
- Modeling and analysis of the macronutrient signaling network in budding yeast.Molecular biology of the cell · 2021Article
- Pib2 as an Emerging Master Regulator of Yeast TORC1.Biomolecules · 2021Review
- A glutamine sensor that directly activates TORC1.Communications biology · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The target of rapamycin (TOR) is a eukaryotic serine/threonine protein kinase that functions in two distinct complexes, TORC1 and TORC2, to regulate growth and metabolism. GTPases, responding to signals generated by abiotic stressors, nutrients, and, in metazoans, growth factors, play an important but poorly understood role in TORC1 regulation. Here we report that, in budding yeast, glucose withdrawal (which leads to an acute loss of TORC1 kinase activity) triggers a similarly rapid Rag GTPase-dependent redistribution of TORC1 from being semi-uniform around the vacuolar membrane to a single, vacuole-associated cylindrical structure visible by super-resolution optical microscopy. Three-dimensional reconstructions of cryo-electron micrograph images of these purified cylinders demonstrate that TORC1 oligomerizes into a higher-level hollow helical assembly, which we name a TOROID (TORC1 organized in inhibited domain). Fitting of the recently described mammalian TORC1 structure into our helical map reveals that oligomerization leads to steric occlusion of the active site. Guided by the implications from our reconstruction, we present a TOR1 allele that prevents both TOROID formation and TORC1 inactivation in response to glucose withdrawal, demonstrating that oligomerization is necessary for TORC1 inactivation. Our results reveal a novel mechanism by which Rag GTPases regulate TORC1 activity and suggest that the reversible assembly and/or disassembly of higher-level structures may be an underappreciated mechanism for the regulation of protein kinases.
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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.