Raptor
Defining subunit of mTORC1: its presence is what makes a complex 'mTORC1', and it is the scaffold that presents substrates (S6K1, 4E-BP1) to mTOR via their TOS motifs. It is also a direct AMPK substrate - AMPK phosphorylates Raptor on two conserved serines, inducing 14-3-3 binding, and that step is required for energy stress to inhibit mTORC1 independently of TSC2 (Gwinn 2008, PMID 18439900). So Raptor is both the substrate-presenting scaffold and one of the two arms by which energy stress reaches mTORC1.
The part that makes mTOR into mTORC1. The defining building block of mTORC1 - it is what makes an mTOR complex 'mTORC1' rather than mTORC2. It holds mTORC1's targets in place so the enzyme can reach them. It is also a brake pedal in its own right: when energy runs low, AMPK tags Raptor directly, and that alone is enough to slow mTORC1 down even if the TSC brake is missing.
Recognises TOS motifs; the AMPK phosphorylation site and the Rag-binding surface both sit here, so Raptor is where location and inhibition converge.
TL;DR. Raptor appears in 21 curated studies in Oliver's mTOR Atlas: 1 in animal models; 20 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| Raptor required-for mTORC1 mechanism: complex-assembly · this link in full · on the map table | Raptor is the piece that makes mTORC1 what it is, and hands it the targets it needs to act on. Holds under: Mostly cell and in vitro work (human cells, C. elegans RNAi, rodent cell lines). One muscle-specific knockout in mice (BEN2008) shows lifelong total loss, which is not the same as partial inhibition by a drug. Not tested in people. plausible in people, not shown directly · settled in the literature | A | HARA2002, KIM2002, BEN2008, SEN2010, NOJ2003 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 1 |
| M | Molecular — cells, biochemistry, structure | 20 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2008 | A | Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy BEN2008 In mice, muscle-specific raptor loss (not rictor) causes dystrophy, showing mTORC1 is essential for muscle homeostasis. |
| 2026 | M | PTEN regulates microtubule polymerization via mTORC2, but not mTORC1, in peripheral sensory neurons EVA2026 Uses Raptor (mTORC1) versus Rictor (mTORC2) co-deletion on a Pten-knockout background to ask which complex carries the growth signal to the microtubule cytoskeleton. Suppressing mTORC2 — but not mTORC1 — returns the accelerated microtubule polymerisation and neuronal hypertrophy of Pten-KO neurons to wild-type levels, and the effect is confined to the axonal growth cone rather than the proximal axon shaft. A clean genetic dissection on the comparatively thin mTORC2 side of the pathway. |
| 2025 | M | Structural basis for mTORC1 activation on the lysosomal membrane CUI2025 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. |
| 2023 | M | Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex CUI2023 First structural view of how mTORC1 actually reaches TFEB to phosphorylate it: two full Rag-Ragulator complexes present a single TFEB molecule to the mTOR active site, one in the normal Raptor-docking arrangement and a second, non-canonical one that grips TFEB's own first helix. Mutating that grip point drives TFEB straight into the nucleus (turning on autophagy/lysosome genes) without disturbing where mTORC1 itself sits. Explains, at the level of atoms, why TFEB phosphorylation needs the tumour suppressor FLCN and the GDP-loaded state of RagC in a way the authors report for no other mTORC1 substrate. Boundary: cryo-EM of a complex reconstituted from purified human proteins — a static structural snapshot, not a live cell or a real-time measurement. |
| 2019 | M | Structural basis for the docking of mTORC1 on the lysosomal surface ROG2019 3.2-angstrom cryo-EM structure of Raptor bound to Rag-Ragulator, showing how Raptor reads out the nutrient-dependent nucleotide state of the Rag GTPases: one part of Raptor senses RagA's nucleotide state, a separate 'claw' senses RagC's, and both have to be in the correct nutrient-signalling combination before Raptor is allowed to dock. Mutating the contact points blocks mTORC1 from reaching the lysosome and inhibits its signalling, which is the functional evidence behind the structural claim. Combined with a separate structure of mTORC1 bound to its activator Rheb, the paper builds a model of the complete, active mTORC1 sitting on the lysosome. Boundary: cryo-EM of a complex reconstituted from purified human proteins, not a live-cell measurement. |
| 2019 | M | Architecture of human Rag GTPase heterodimers and their complex with mTORC1 ANA2019 Structures of Rag GTPase heterodimers with mTORC1 explain nucleotide-state-dependent recruitment. |
| 2016 | M | Dynamics of mTORC1 activation in response to amino acids MAN2016 Live imaging shows mTORC1 moves to lysosomes within 2 minutes of amino acid addition and peaks by 5 minutes, in step with leucine arriving in lysosomes; phosphorylation of classic mTORC1 targets lags behind, suggesting mTORC1 passes briefly through the lysosome before acting on substrates elsewhere. |
| 2016 | M | Tor forms a dimer through an N-terminal helical solenoid with a complex topology BAR2016 Cryo-EM shows TOR dimerizes through an N-terminal helical solenoid, informing mTORC1 architecture. |
| 2015 | M | Architecture of human mTOR complex 1 AYL2015 Cryo-EM architecture of human mTORC1 reveals its dimeric organization and active site access. |
| 2010 | M | mTORC1 controls fasting-induced ketogenesis and its modulation by ageing SEN2010 mTORC1 controls fasting-induced hepatic ketogenesis via PPARalpha, and this is blunted with age. |
| 2010 | M | Structure of the human mTOR complex I and its implications for rapamycin inhibition YIP2010 The authors purified intact, active human mTORC1 and solved its shape by cryo-electron microscopy at about 26 angstrom resolution. The complex is an obligate dimer with a rhomboid outline and a central cavity, held together by interlocking contacts between mTOR and Raptor; antibody labelling placed mLST8 at the outer 'feet' and PRAS40 next to Raptor. Exposing purified mTORC1 to FKBP12-rapamycin first added a bound density in about 10% of particles, then broke the complex apart, with virtually no intact particles left after one hour, while the ATP-competitive inhibitor Torin1 left it intact. In matching kinase assays, FKBP12-rapamycin blocked S6K1 phosphorylation quickly but 4E-BP1 phosphorylation only after at least 60 minutes, and Raptor-free mTOR still phosphorylated S6K1 (rapamycin-sensitively) but not 4E-BP1. The authors proposed that rapamycin inhibits the two substrates by different mechanisms. Boundary: Purified protein and low-resolution EM; the authors note that in cells rapamycin neither fully blocks 4E-BP1 phosphorylation nor dismantles mTORC1, so the disassembly model is an in vitro result. |
| 2008 | M | AMPK phosphorylation of raptor mediates a metabolic checkpoint GWI2008 Found a SECOND way the energy sensor AMPK shuts mTORC1 down. Besides acting through TSC2, AMPK directly phosphorylates Raptor - the core mTORC1 subunit - to halt growth when energy runs low. This 'metabolic checkpoint' is exactly the switch that drugs like metformin and exercise tap into. |
| 2007 | M | PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase SAN2007 Identified PRAS40 as the missing insulin-controlled brake INSIDE mTORC1. When insulin is absent PRAS40 clamps the complex shut; insulin makes Akt phosphorylate PRAS40, releasing the brake so Rheb can fully switch mTORC1 on. Explained how hormone signals set the exact strength of mTORC1 activity. |
| 2007 | M | mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex CUN2007 Showed mTOR isn't just about building proteins - it also runs the cell's POWER plants. mTORC1 drives mitochondrial gene expression and oxygen consumption through a YY1-PGC-1alpha transcriptional program; block mTOR with rapamycin and mitochondrial output falls. Explains part of why mTOR inhibition reshapes metabolism. |
| 2006 | M | Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 GUE2006 The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice. |
| 2006 | M | The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity SCH2006 In human cultured cells, the amount of mTOR-raptor complex correlated with overall mitochondrial activity. Disrupting the complex with rapamycin lowered mitochondrial membrane potential, oxygen consumption and ATP-synthetic capacity. mTOR and mTOR-raptor complexes were found in purified mitochondrial fractions, and rapamycin markedly changed the mitochondrial phosphoproteome. RNA interference against TSC2, S6K1, raptor or rictor led the authors to conclude that mTOR regulates mitochondrial activity independently of its previously known targets, and they proposed that mTOR activity shifts the balance between mitochondrial and non-mitochondrial ATP production. Boundary: Cultured human cell line with acute pharmacological and RNAi manipulation; the link to lifespan is a hypothesis drawn from lower organisms, not tested here. Drafted from the abstract only. |
| 2005 | M | Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase NOB2005 The companion paper to BYF2005, from a different laboratory: the amino acid input to mTORC1 is separate from the insulin input and runs through class 3 PI3K (hVps34), not through class 1 PI3K. Historically important because it states that the amino acid branch is the older one and that insulin signalling was grafted onto it. Boundary: cell lines, pharmacological and knockdown evidence; the later Rag/Ragulator account describes a different route to the same target, and the two accounts are not reconciled in the work this Atlas holds. |
| 2003 | M | GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR KIM2003 Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex. |
| 2003 | M | The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif NOJ2003 Raptor binds mTOR substrates via their TOS motifs, acting as the substrate-presenting scaffold of mTORC1. |
| 2002 | M | mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery KIM2002 Discovery of Raptor as the defining partner of mTOR in mTORC1. This is the paper that gives mTORC1 its identity: Raptor is the scaffold that lets mTOR find and phosphorylate its targets (S6K1), and the complex is stabilized under starvation. Companion paper to Hara 2002. |
| 2002 | M | Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action HARA2002 Independent co-discovery of Raptor (same issue of Cell as Kim 2002). Showed Raptor is essential for mTOR to phosphorylate 4E-BP1 and S6K1, and that knocking it down in worms mimics loss of TOR - confirming Raptor as a core, conserved mediator of TOR action. |
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