DCAR-1 (C. elegans) — research notes
UniProt: G5EDI0 (G5EDI0_CAEEL) · WormBase: WBGene00007395 · sequence name C06H5.7 ·
Reactome: R-CEL-416476 "G alpha (q) signalling events" · 396 aa, 7-TM class A (rhodopsin-like)
GPCR (PROSITE PS50262 G_PROTEIN_RECEP_F1_2; PANTHER PTHR24243). Chromosome V.
DCAR-1 = "DihydroCaffeic Acid Receptor 1". Two distinct, experimentally established
functional contexts, in two tissues:
- Epidermal innate immunity (flagship function; Zugasti et al. 2014, Nat Immunol,
PMID:25086774). DCAR-1 is a plasma-membrane GPCR on the apical surface of the hyp7
epidermal syncytium that senses the endogenous tyrosine-derived metabolite HPLA
(4-hydroxyphenyllactic acid, a damage-associated molecular pattern, DAMP) produced upon
fungal infection/wounding, and triggers antimicrobial-peptide (nlp-29 cluster) gene
expression via the GPA-12 (Gα) → TIR-1 → NSY-1/SEK-1/PMK-1 (p38 MAPK) → STA-2 cascade in
the epidermis. Required for resistance to the fungus Drechmeria coniospora.
- Neuronal chemosensory avoidance (Aoki et al. 2011, J Neurosci, PMID:22090488).
DCAR-1 was originally identified in a Xenopus oocyte expression screen as a receptor
for the water-soluble repellent dihydrocaffeic acid (DHCA); expressed in the ASH (and
ASI, PVQ) sensory neurons, where it mediates avoidance of DHCA acting with ocr-2/osm-9.
KNOWN (well supported)
- 7-TM class A GPCR. UniProt/InterPro: 7 predicted TM helices, GPCR family 1 profile
domain (PS50262), CDD 7tm_classA_rhodopsin-like, PANTHER PTHR24243. FunFam name
"DihydroCaffeic Acid Receptor". Reactome links it to "G alpha (q) signalling events".
- Innate immune receptor. PMID:25086774 Sole
hit from an RNAi screen of 1,150 GPCR genes for reduced nlp-29p::gfp AMP induction; two
null alleles (tm2484, nj66) confirm. dcar-1 mutants are markedly more susceptible to
D. coniospora while having normal development/longevity and normal resistance to
P. aeruginosa.
- Acts via p38 MAPK / GPA-12 in epidermis. PMID:25086774 PMID:25086774. Methods list gpa-12(pk322), tir-1(tm3036), pmk-1(km25),
tpa-1(fr1) epistasis strains — this is the GPA-12→TIR-1→p38/PMK-1 cassette. Links to the
already-reviewed gpa-12 (Gα12/13 ortholog).
- Endogenous ligand = HPLA (a DAMP). PMID:25086774. Identified by comparative
metabolomics: HPLA present at low level in controls, increased upon infection and in
cuticle-defective dpy-10 mutants. PMID:25086774. PMID:25086774
- Exogenous ligand = DHCA. PMID:25086774.
Original identification: PMID:22090488
- Localization. Apical plasma membrane in hyp7 epidermis:
PMID:25086774 (IDA, GO:0016324). Neuronal expression in ASH/ASI/PVQ (ciliated sensory
neurons); WormBase IDA GO:0097730 non-motile cilium from PMID:22090488 (abstract-only in
cache; the cilium sub-localization is not stated in the abstract but was curated by
WormBase from the full text — trust the curator).
- Response to wounding. PMID:25086774 dcar-1 mutants show "an almost complete block of
nlp-29p::gfp induction following physical injury", i.e. activation is damage/wound-dependent
even without a pathogen (GO:0009611 response to wounding, IMP).
- Cell-autonomous, tissue-separable. Epidermal (col-12p) but not neuronal (sra-6p)
expression rescues AMP induction/immunity; conversely neuronal expression rescues the
avoidance phenotype. PMID:25086774.
- Phylogenetically nematode-restricted. PMID:25086774.
NOT known / open (for knowledge_gaps)
- Structural basis of HPLA/DHCA sensing is unknown. No direct binding data, no structure,
and the ligand-binding pocket / residues are undefined. HPLA binding is inferred from
correlative genetics + metabolomics, not a direct receptor-binding assay:
PMID:25086774. Whether DCAR-1 is even the
direct HPLA receptor (vs an upstream sensor) is not biochemically proven.
- Whether DCAR-1 has other (neuropeptide or microbial) ligands / roles is unknown. Its
natural neuronal ligand and whether it detects any microbe-associated molecular pattern are
undetermined: PMID:25086774 A speculated second role in pathogen-avoidance
behavior is unproven.
- HPLA biosynthesis / how infection raises HPLA is uncharacterized. PMID:25086774; whether the fungus contributes to HPLA or it is purely host
damage-derived is an open question.
- Nematode-restricted receptor with a conserved-metabolite ligand — whether an
HPLA/DAMP-sensing receptor exists outside nematodes is unknown: PMID:25086774
Annotation review plan (existing_annotations)
| term |
ev |
ref |
action |
rationale |
| GO:0004930 G protein-coupled receptor activity |
IEA |
GO_REF:0000104 |
ACCEPT (core MF) |
7-TM class A GPCR; receptor for HPLA/DHCA |
| GO:0007186 GPCR signaling pathway |
IEA |
GO_REF:0000104 |
ACCEPT (core BP) |
signals via GPA-12 Gα |
| GO:0007165 signal transduction |
IEA |
GO_REF:0000104 |
KEEP_AS_NON_CORE |
correct but generic parent of GPCR signaling |
| GO:0050832 defense response to fungus |
IMP |
PMID:25086774 |
ACCEPT (core BP) |
required for anti-D. coniospora defense |
| GO:0009611 response to wounding |
IMP |
PMID:25086774 |
ACCEPT (core BP) |
wound/damage-activated AMP induction |
| GO:0016324 apical plasma membrane |
IDA |
PMID:25086774 |
ACCEPT (core CC) |
apical hyp7 surface |
| GO:0005886 plasma membrane |
IBA |
GO_REF:0000033 |
ACCEPT |
correct (parent of apical PM) |
| GO:0016020 membrane |
IEA |
GO_REF:0000120 |
KEEP_AS_NON_CORE |
generic; subsumed by apical PM |
| GO:0097730 non-motile cilium |
IDA |
PMID:22090488 |
KEEP_AS_NON_CORE |
neuronal (ASH) chemosensory localization; abstract-only cache, defer to WB curator |
| GO:0008188 neuropeptide receptor activity |
IBA |
GO_REF:0000033 |
REMOVE |
over-propagated family IBA; DCAR-1 ligands are small-molecule metabolites (HPLA/DHCA), not neuropeptides |
| GO:0007218 neuropeptide signaling pathway |
IBA |
GO_REF:0000033 |
REMOVE |
same; not a neuropeptide receptor |
Proposed new term candidate: a specific MF for "dihydroxyphenyl/hydroxyphenyllactic acid
(DAMP) receptor activity" — currently only GO:0004930 available. Note as ontology gap.
Deep research provenance
The just deep-research-falcon recipe reported a 600s timeout on both the initial run and
the retry (and the perplexity-lite fallback returned HTTP 401, quota exhausted). However the
underlying Edison/falcon client kept running and, on the retry, DID write a genuine report
(dcar-1-deep-research-falcon.md, ~1005s runtime, 19 citations, 2 artifacts) after the
recipe's wrapper had already exited. That file was inspected and is authentic Edison output:
it correctly identifies DCAR-1, HPLA as the DAMP ligand, apical hyp7 epidermal localization,
and the full GPA-12 -> PLC/DAG -> TPA-1(PKC) -> TIR-1 -> NSY-1/SEK-1/PMK-1(p38) -> STA-2/ELT-3
-> nlp-29 pathway, plus the neuronal DHCA-avoidance origin. It is included in the commit and
referenced. No -deep-research-*.md file was fabricated.
All annotation/core-function supporting_text quotes are PMID-anchored (verified as verbatim
whitespace-normalized substrings of PMID:25086774 full text and PMID:22090488 abstract). The
single file: deep-research quote used was grep-verified against the falcon report (the
reference validator skips file: prefixes).