Pathway link RAG-MTORC1
Rag GTPases mTORC1
Rag GTPases recruits mTORC1.
The switched-on Rag proteins grab mTORC1 and drag it to the lysosome. This moves it into place; it doesn't turn it on by itself.
The conditions it holds under
Rag paralogues are not interchangeable: RagC/D sets substrate specificity downstream (RagD favors TFEB/TFE3 phosphorylation via tighter LAMTOR binding, while both Rags are involved for non-lysosomal substrates like S6K), and RagA/B sets the response to amino acid withdrawal (RagB-expressing cells keep mTORC1 lysosomal and active even when starved) — GOL2022.
- Time it takes
- minutes
- Step
- direct (one molecule acts on the other)
- Measured in
- human cells
- Where in the cell
- lysosome
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2008 | M | The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1SAN2008 Identifies the Rag GTPase family as the missing link that lets mTORC1 sense amino acids by controlling whether mTOR is positioned near its activator Rheb. |
| 2010 | M | Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acidsSAN2010 Established WHERE mTORC1 gets switched on: the lysosome surface. Identified Ragulator as the lysosomal dock that recruits the Rag GTPases and drags mTORC1 to the membrane where its activator Rheb lives. Amino acids work by controlling this translocation. |
| 2018 | M | A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffoldLAW2018 A nutrient-induced affinity switch in the Rag-Ragulator scaffold controls mTORC1 lysosomal recruitment. |
| 2022 | M | A Rag GTPase dimer code defines the regulation of mTORC1 by amino acidsGOL2022 The four mammalian Rag GTPase paralogues are not functionally interchangeable: RagC/D determines substrate specificity (RagD favors TFEB/TFE3 phosphorylation via tighter LAMTOR binding), while RagA/B determines the response to amino acid withdrawal (RagB-expressing cells keep mTORC1 lysosomal and active even upon starvation). Author correction issued 2023 (PMID 36536178, no change to conclusions). |
| 2012 | A | Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survivalEFE2012 Rag-GTPase control of mTORC1 is essential for neonatal autophagy and survival to fasting. |
| 2025 | M | Structural basis for mTORC1 activation on the lysosomal membraneCUI2025 Resolves how mTORC1 flips from 'parked on the lysosome' to 'catalytically switched on'. Reconstituting the whole assembly on membranes from purified Rheb, Rag GTPases, Ragulator and mTORC1, cryo-EM shows the kinase reaches full activity only after two separate anchoring steps: Rag-Ragulator first pulls it to within about 100 angstroms of the membrane, then Rheb pulls it to within about 40 angstroms, and only when Raptor and mTOR itself also touch the membrane directly do the catalytic residues line up for full activity. Growth-factor input (via Rheb) and nutrient input (via the Rags) are shown converging on the same physical docking event rather than acting through separate switches. Boundary: reconstituted on synthetic membranes from purified components — a structural/biochemical model, not a measurement inside a living cell. |
| 2011 | M | Spatial coupling of mTOR and autophagy augments secretory phenotypesNAR2011 Protein synthesis and autophagic degradation are usually described as opposites that mTOR switches between, and this paper shows a compartment where the cell deliberately runs both at once. In senescent cells, autolysosomes and mTOR gather at one side of the Golgi (the TASCC), mTOR gets there in an amino-acid- and Rag-dependent way, and destroying that arrangement cuts interleukin-6/8 secretion. Boundary: cells, not organisms; it explains how the senescent secretory programme is fuelled, not whether blocking it helps an animal. |
| 2008 | M | Regulation of TORC1 by Rag GTPases in nutrient responseKIM2008 Rag GTPases mediate amino-acid signalling to TORC1 (parallel discovery to Sancak 2008). |
| 2019 | M | Architecture of human Rag GTPase heterodimers and their complex with mTORC1ANA2019 Structures of Rag GTPase heterodimers with mTORC1 explain nucleotide-state-dependent recruitment. |
| 2012 | M | SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signalingKIM2012 SH3BP4 negatively regulates amino-acid-Rag-GTPase-mTORC1 signalling. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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