daf-15 encodes the Caenorhabditis elegans ortholog of Raptor (regulatory-associated protein of mTOR), a large (1782 aa) non-catalytic scaffold built from an N-terminal Raptor N-terminal CASPase-like (RNC) domain, a central ARM/HEAT-like repeat region and a C-terminal WD40 propeller. By orthology with mammalian and yeast Raptor/Kog1 it is the defining subunit of TOR complex 1 (TORC1), binding the LET-363/TOR kinase and presenting TORC1 substrates such as RSKS-1/S6K and the translational repressor pathway, and docking the complex on the lysosomal Rag GTPase platform; a DAF-15 fusion carrying the RAP-1 C-terminal lysosome-targeting signal constitutively activates TORC1 signaling in vivo. DAF-15/TORC1 signaling couples nutrient availability to postembryonic growth: daf-15 loss-of-function causes a non-recoverable dauer-like larval arrest, intestinal fat accumulation and small nucleoli, reduced TORC1 activity limits the germline progenitor pool, and partial reduction extends adult lifespan in a pha-4/FoxA-dependent manner. daf-15 transcription is repressed by DAF-16/FOXO, providing a point of convergence between insulin/IGF-1 signaling and nutrient sensing.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008340 determination of adult lifespan | IGI PMID:18804378 The Target of Rapamycin pathway antagonizes pha-4/FoxA to co... | KEEP AS NON CORE | Summary: Combined let-363(RNAi); daf-15(RNAi) from L4 extends adult lifespan, and this extension depends on pha-4/FoxA (WBGene00002583, the IGI partner). Jia et al. 2004 independently report that raptor mutations extend lifespan. The term is a genuine organismal output of DAF-15/TORC1 signaling but is downstream of the core signaling activity, so it is kept as non-core. Reason: Well supported genetic evidence (full text read) that reduced DAF-15/TORC1 activity extends lifespan via pha-4; lifespan is an organismal consequence of TORC1 signaling rather than the molecular role of Raptor. Supporting Evidence: PMID:18804378 Reduction of let-363 and daf-15 together led to a statistically-significant increase in lifespan in 3/4 experiments PMID:18804378 Strikingly, pha-4(ts); let-363(RNAi); daf-15(RNAi) animals had shorter life spans than pha-4(ts) alone. PMID:15253933 raptor mutations extend adult life span |
| GO:0031929 TOR signaling | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the Raptor family signature (IPR004083). The claim is correct, but Raptor is the defining subunit of TORC1 (it is absent from TORC2, which uses Rictor/RICT-1), so the specific child term TORC1 signaling (GO:0038202) is warranted. Worm evidence: DAF-15 is listed among the C. elegans TORC1 components, and a DAF-15::RAP-1(22) fusion hyperactivates TORC1 signaling in vivo. Reason: Correct but general. Raptor-containing signaling is by definition TORC1 signaling (GO:0038202 definition names Raptor), so refine to that is_a child. Proposed replacements: TORC1 signaling Supporting Evidence: file:worm/daf-15/daf-15-uniprot.txt IPR004083; Raptor PMID:18804378 C. elegans possesses homologues of TOR complex 1 (TORC1) components, including TOR kinase (let-363 [21]), Raptor (daf-15; [15]) and LST8 PMID:23705068 This indicates that hyperactivation of TORC1 was sufficient to support L1 growth in mmBCFA-depleted animals. |
| GO:0031931 TORC1 complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the Raptor family signature. Raptor is the defining subunit of TORC1 in all eukaryotes examined, and DAF-15 carries the full RNC/ARM/WD40 architecture of Raptor. Accepted as the core complex membership. Reason: Family membership (IPR004083 Raptor, PANTHER PTHR12848) plus worm genetic and transgenic evidence that DAF-15 acts as a TORC1 component. Supporting Evidence: file:worm/daf-15/daf-15-uniprot.txt IPR004083; Raptor PMID:18804378 C. elegans possesses homologues of TOR complex 1 (TORC1) components, including TOR kinase (let-363 [21]), Raptor (daf-15; [15]) and LST8 |
| GO:0031931 TORC1 complex | ISS GO_REF:0000024 | ACCEPT | Summary: WormBase sequence-similarity transfer from human RPTOR (Q8N122), whose TORC1 membership is experimentally established. Consistent with the IEA row; the orthology is unambiguous (single Raptor gene in C. elegans, same domain architecture). Reason: Sound orthology transfer for a defining complex subunit; in vivo DAF-15::RAP-1(22) fusion behaves as a TORC1 activator, as Raptor-Rap1 fusions do in mammalian cells. Supporting Evidence: file:worm/daf-15/daf-15-deep-research-manual.md Ortholog of human RPTOR (Q8N122), Drosophila raptor, yeast KOG1. PMID:23705068 fusion of one of the TOR binding partners, Raptor, with a C-terminal lysosome localization signal from Rap-1 can localize mTOR to the lysosome and thus constitutively activate the TOR pathway PMID:23705068 We fused a 22-amino acid fragment of the C-terminal end of rap-1 to the C-terminal end of daf-15 and named it daf-15::rap-1(22). |
| GO:0040024 dauer larval development | IMP PMID:3350212 Mutants of Caenorhabditis elegans that form dauer-like larva... | KEEP AS NON CORE | Summary: daf-15(m81) animals constitutively enter an incomplete, non-recoverable dauer-like state and are epistatic to dauer-defective mutations (abstract only; full text not cached). Jia et al. 2004 confirm that raptor and CeTOR mutations cause dauer-like larval arrest. The phenotype reflects loss of nutrient-driven TORC1 growth signaling that normally promotes reproductive development; DAF-15 regulates the dauer decision rather than executing dauer morphogenesis. Kept as non-core, deferring to the curator's reading of the full text. Reason: Experimental IMP annotation consistent with independent evidence; a developmental consequence of TORC1 signaling, peripheral to Raptor's molecular role. Supporting Evidence: PMID:3350212 Dauer larva morphogenesis is initiated regardless of environmental stimuli, and it is incomplete or abnormal. PMID:15253933 mutations in the genes encoding CeTOR and raptor result in dauer-like larval arrest, implying that CeTOR regulates dauer diapause |
| GO:0030674 protein-macromolecule adaptor activity | ISS GO_REF:0000024 | NEW | Summary: DAF-15 has no molecular-function annotation. Raptor's established activity is that of a scaffold/adaptor that binds TOR and recruits TORC1 substrates (TOS-motif proteins such as S6K and 4E-BP) and the Rag GTPases. DAF-15 shares the full Raptor architecture, and the in vivo DAF-15::RAP-1(22) experiment shows DAF-15 can bring TORC1 to the lysosome as mammalian Raptor does. Proposed by sequence similarity to human RPTOR. Reason: Captures the core molecular role of Raptor, the only function DAF-15 itself performs within TORC1 signaling; consistent with the DROME raptor review. No worm biochemistry (binding assays) exists, hence ISS. Supporting Evidence: file:worm/daf-15/daf-15-uniprot.txt IPR004083; Raptor PMID:23705068 fusion of one of the TOR binding partners, Raptor, with a C-terminal lysosome localization signal from Rap-1 can localize mTOR to the lysosome and thus constitutively activate the TOR pathway |
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Download this section (compressed HTML)Q: Does DAF-15 bind LET-363/TOR and TOS-motif substrates (RSKS-1, IFE/4E-BP pathway components) directly in C. elegans, as Raptor does in mammals, or is the adaptor activity inferred only by orthology?
Q: Is DAF-15 lysosome-associated in vivo under fed conditions via RAGA-1/RAGC-1, and how does DAF-16-mediated transcriptional repression of daf-15 change TORC1 localization or activity?
Experiment: Co-immunoprecipitation of endogenously tagged DAF-15 with LET-363 and RSKS-1 from fed versus starved worms, with RNC-domain point mutants predicted to disrupt TOS-motif binding.
Experiment: Live imaging of CRISPR-tagged DAF-15 with a lysosomal marker (LMP-1) across feeding states and in raga-1 mutants.
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Download this section (compressed HTML)daf-15 encodes an ortholog of RAPTOR (the regulatory associated proteinof mTOR), and is regulated by DAF-16; daf-15 is required for non-dauerdevelopment, at least in some tissues or stages; daf-15(m81) mutantsconstitutively and irreversibly form abnormal dauer-like larvae (and arethus effectively lethal/sterile); mutants do not form true dauers whenexposed to dauer pheromone, yet execute only two molts.
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