OCR-2 (OSM-9 and Capsaicin Receptor-related 2) is a TRPV (Transient Receptor Potential Vanilloid) family cation channel subunit that functions as part of a heteromeric complex with OSM-9 in C. elegans sensory neurons. The OCR-2/OSM-9 heteromeric channel is essential for multiple sensory modalities including thermosensation, chemosensation, osmosensation, and nociception. The channel localizes to the sensory cilia of amphid neurons (including ADL, ASH, AWA, ADF) where it mediates sensory transduction. OCR-2/OSM-9 is directly activated by warming stimuli and functions as an accessorial warm receptor contributing to temperature acclimatization. The channel also regulates serotonin biosynthesis in ADF neurons. Neither OCR-2 nor OSM-9 alone is sufficient for heat-evoked currents; functional channels require co-expression of both subunits. The channel displays outward-rectifying current-voltage characteristics typical of TRPV channels.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005262 calcium channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: OCR-2/OSM-9 heteromeric TRPV channel conducts calcium and other cations. Electrophysiology in Xenopus oocytes demonstrates warming-evoked inward currents with outward-rectifying I-V relationships when both subunits are co-expressed (PMID:33122746). The channel is a member of the TRP-CC family per TCDB (1.A.4.3.3). While "calcium channel activity" is correct, the more specific term GO:0097604 (temperature-gated cation channel activity) better captures the functional mode of gating. Reason: IBA annotation is phylogenetically appropriate for TRPV family membership. OCR-2 is a bona fide calcium-permeable channel as demonstrated by electrophysiology studies showing warming-evoked inward currents in oocytes co-expressing OSM-9 and OCR-2 (PMID:33122746). The UniProt record also indicates calcium channel and calcium transport keywords. Supporting Evidence: PMID:33122746 Thermal stimuli evoked inward currents in Xenopus oocytes co-expressing OSM-9 and OCR-2 PMID:12160748 Both OSM-9 and OCR-2 are essential for several forms of sensory transduction, including olfaction, osmosensation, mechanosensation, and chemosensation |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: OCR-2 localizes to the plasma membrane of sensory cilia. Studies show OCR-2 and OSM-9 co-localize in sensory cilia and promote each other's localization to cilia (PMID:12160748). More specifically, OCR-2 is found in the non-motile (sensory) cilia of amphid neurons. Reason: IBA annotation is appropriate. OCR-2 is a multi-pass transmembrane protein that localizes to the plasma membrane of sensory cilia. The UniProt record confirms cell membrane localization with multi-pass membrane topology. Supporting Evidence: PMID:12160748 In neurons that express both OSM-9 and OCR-2, tagged OCR-2 and OSM-9 proteins reside in sensory cilia and promote each other's localization to cilia PMID:15673683 OCR-2 function in 5-HT production and osmotic sensing is governed by its N-terminal region upstream of the ankyrin repeats domain |
| GO:0098703 calcium ion import across plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: As a calcium-permeable TRP channel in the plasma membrane, OCR-2/OSM-9 mediates calcium influx upon activation. This is consistent with the sensory transduction function where calcium entry is part of signal transduction. Reason: IBA annotation is appropriate as a consequence of calcium channel activity at the plasma membrane. The warming-evoked inward currents observed in oocytes are consistent with cation (including calcium) influx (PMID:33122746). Supporting Evidence: PMID:33122746 Thermal stimuli evoked inward currents in Xenopus oocytes co-expressing OSM-9 and OCR-2 |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: OCR-2 contains the Ion_trans domain (IPR005821) and functions as an ion channel. This general term is consistent with TRPV channel function but is redundant with more specific calcium channel activity annotation. Reason: IEA based on InterPro domain annotation is correct but very general. The ion transport domain (Pfam PF00520) is present from residues 517-771 per UniProt. While redundant with calcium channel activity, this broad term is not incorrect. |
| GO:0005262 calcium channel activity | IEA GO_REF:0000043 | ACCEPT | Summary: IEA based on UniProt keyword mapping. This duplicates the IBA annotation but through different evidence. The annotation is consistent with OCR-2's demonstrated function. Reason: Redundant with IBA annotation but correct. UniProt keywords include "Calcium channel" which supports this mapping. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA based on UniProt subcellular location. Duplicates the IBA annotation. Reason: Redundant with IBA annotation but correct. UniProt subcellular location states "Cell membrane; Multi-pass membrane protein." |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000120 | ACCEPT | Summary: General ion transport term. OCR-2 transports cations including calcium as part of sensory signaling. This is a parent term of more specific transport processes. Reason: While very general, this is not incorrect. OCR-2 mediates ion transport as a TRPV channel subunit. More specific annotations (calcium ion transport) also exist. |
| GO:0006816 calcium ion transport | IEA GO_REF:0000043 | ACCEPT | Summary: Calcium ion transport is a consequence of calcium channel activity. OCR-2/OSM-9 mediates calcium influx during sensory transduction. Reason: Appropriate IEA based on UniProt calcium transport keyword. Consistent with calcium channel function. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Very general localization term based on transmembrane domains. OCR-2 has 6-7 transmembrane helices per UniProt feature annotations. This is redundant with more specific plasma membrane annotation. Reason: While overly general, this is not incorrect. OCR-2 is a multi-pass membrane protein with transmembrane helices at positions 426-445, 517-538, 550-573, 585-606, 613-630, 636-654, and 738-760 per UniProt. |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000043 | ACCEPT | Summary: Ion transmembrane transport is the expected outcome of ion channel activity. This is consistent with OCR-2 function. Reason: Correct but general. OCR-2/OSM-9 channels mediate transmembrane ion flux during sensory signaling. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Very general transport term. OCR-2 mediates transmembrane transport of cations. Reason: While overly general, this is not incorrect for a transmembrane channel protein. More specific annotations exist. |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000043 | ACCEPT | Summary: Calcium ion transmembrane transport is the specific outcome of calcium channel activity at the plasma membrane. Reason: Appropriate specificity level for a calcium-permeable channel. Consistent with demonstrated electrophysiology showing cation currents. |
| GO:0010286 heat acclimation | IDA PMID:33122746 OSM-9 and OCR-2 TRPV channels are accessorial warm receptors... | ACCEPT | Summary: Ohnishi et al. (2020) demonstrated that OSM-9/OCR-2 TRPV channels function as accessorial warm receptors required for temperature acclimatization. TRPV mutants (osm-9, ocr-2) showed abnormal temperature acclimatization with elevated cold tolerance. The defect was partially rescued by expression of cDNA in ADL neurons. Reason: Well-supported experimental evidence. The paper directly demonstrates OCR-2's role in temperature acclimatization through mutant analysis, rescue experiments, and functional reconstitution studies. This represents a core biological process function. Supporting Evidence: PMID:33122746 OSM-9/OCR-2 regulates temperature acclimatisation and acts as an accessorial warmth-sensing receptor in ADL neurons PMID:33122746 The abnormally elevated cold tolerance of osm-9 and ocr-2 mutants was partially rescued by expression of osm-9 and ocr-2 cDNA in ADL, respectively |
| GO:0010286 heat acclimation | IMP PMID:33122746 OSM-9 and OCR-2 TRPV channels are accessorial warm receptors... | ACCEPT | Summary: Mutant phenotype evidence for heat acclimation role. ocr-2 mutants show abnormal temperature acclimatization behavior with elevated cold tolerance compared to wild-type animals. Reason: Valid IMP evidence from mutant analysis. The osm-9 and ocr-2 mutants display abnormal cold tolerance/temperature acclimatization phenotypes that are partially rescued by transgenic expression. Supporting Evidence: PMID:33122746 Caenorhabditis elegans TRPV channel mutants showed abnormal temperature acclimatisation |
| GO:0010286 heat acclimation | IGI PMID:33122746 OSM-9 and OCR-2 TRPV channels are accessorial warm receptors... | ACCEPT | Summary: Genetic interaction evidence. OSM-9 and OCR-2 function cooperatively, and their combined activity is required for heat acclimation. Neither single subunit alone produces functional warming responses. Reason: Valid IGI evidence demonstrating functional interaction between OCR-2 and OSM-9. The double mutant and reconstitution studies show cooperative function. Supporting Evidence: PMID:33122746 OSM-9 and OCR-2 cooperatively responded to warming; however, neither TRPV subunit alone was responsive to warming |
| GO:0097604 temperature-gated cation channel activity | IDA PMID:33122746 OSM-9 and OCR-2 TRPV channels are accessorial warm receptors... | ACCEPT | Summary: Direct experimental evidence from electrophysiology in Xenopus oocytes and in vivo reconstitution. Co-expression of OSM-9 and OCR-2 produces warming-evoked currents. Ectopic expression in non-temperature-sensing neurons conferred temperature responsiveness. Reason: This is the most precise molecular function annotation for OCR-2/OSM-9. The heterologous expression studies and in vivo reconstitution directly demonstrate temperature-gated channel activity. This should be considered the primary molecular function annotation. Supporting Evidence: PMID:33122746 Thermal stimuli evoked inward currents in Xenopus oocytes co-expressing OSM-9 and OCR-2 PMID:33122746 Ectopic expression of OSM-9 and OCR-2 in non-warming-responsive gustatory neurons in C. elegans and Xenopus oocytes revealed that OSM-9 and OCR-2 cooperatively responded to warming |
| GO:0005886 plasma membrane | IDA PMID:15673683 Polymodal sensory function of the Caenorhabditis elegans OCR... | ACCEPT | Summary: Sokolchik et al. (2005) characterized OCR-2 function in its native cellular environment, demonstrating polymodal sensory function at the plasma membrane of sensory neurons. Reason: IDA evidence for plasma membrane localization from functional studies showing OCR-2 activity in membrane-associated sensory processes. Supporting Evidence: PMID:15673683 we identify the molecular basis for the polymodal function of OCR-2 in its native cellular environment |
| GO:0097730 non-motile cilium | IDA PMID:15673683 Polymodal sensory function of the Caenorhabditis elegans OCR... | ACCEPT | Summary: OCR-2 localizes to non-motile sensory cilia of amphid neurons. The sensory cilia of C. elegans chemosensory and thermosensory neurons are non-motile primary cilia used for environmental sensing. Reason: Appropriate localization annotation. C. elegans sensory neurons have non-motile cilia where TRPV channels reside. OCR-2 function in sensory transduction occurs at these ciliary structures. Supporting Evidence: PMID:12160748 In neurons that express both OSM-9 and OCR-2, tagged OCR-2 and OSM-9 proteins reside in sensory cilia and promote each other's localization to cilia |
| GO:0097730 non-motile cilium | IDA PMID:12160748 Combinatorial expression of TRPV channel proteins defines th... | ACCEPT | Summary: Tobin et al. (2002) directly demonstrated that tagged OCR-2 and OSM-9 proteins reside in sensory cilia and promote each other's localization to cilia. This study established the ciliary localization paradigm for C. elegans TRPV channels. Reason: Key primary evidence for ciliary localization. The study used tagged proteins to directly visualize OCR-2 in sensory cilia and showed that OCR-2 and OSM-9 are codependent for proper ciliary localization. Supporting Evidence: PMID:12160748 In neurons that express both OSM-9 and OCR-2, tagged OCR-2 and OSM-9 proteins reside in sensory cilia and promote each other's localization to cilia PMID:12160748 In neurons that express only OSM-9, tagged OSM-9 protein resides in the cell body and acts in sensory adaptation rather than sensory transduction |
| GO:0007635 chemosensory behavior | IMP PMID:12160748 Combinatorial expression of TRPV channel proteins defines th... | NEW | Summary: OCR-2 mutants have defects in chemosensory behaviors. Tobin et al. (2002) showed that OSM-9 and OCR-2 are essential for olfaction, chemosensation, and responses to chemical stimuli. The ocr-2 mutation affects response to diacetyl in AWA neurons. Reason: Critical biological process annotation missing from existing GOA. The deep research clearly documents OCR-2's role in chemosensory behavior, particularly in AWA-mediated olfaction and ASH-mediated nociception to chemicals like 1-octanol. Supporting Evidence: PMID:12160748 Both OSM-9 and OCR-2 are essential for several forms of sensory transduction, including olfaction, osmosensation, mechanosensation, and chemosensation PMID:15673683 the diacetyl sensitivity is mediated by independent mechanisms file:worm/ocr-2/ocr-2-deep-research-falcon.md OCR-2 functions with OSM-9 in multiple sensory neurons. In ADL, OSM-9/OCR-2 mediate warmth responses... In nociceptive contexts, a heteromeric OSM-9/OCR-2 channel is required for aversive chemical responses such as to 1-octanol |
| GO:0009593 detection of chemical stimulus | IMP PMID:15673683 Polymodal sensory function of the Caenorhabditis elegans OCR... | NEW | Summary: OCR-2 is a polymodal sensory channel that responds to multiple stimuli including temperature, chemicals, and osmotic changes. Sokolchik et al. (2005) demonstrated the polymodal nature of OCR-2 function in chemical detection. Reason: This captures OCR-2's fundamental role in sensory transduction for chemical stimuli. Sokolchik et al. (2005) demonstrated the polymodal nature of OCR-2 function. Supporting Evidence: PMID:15673683 Caenorhabditis elegans OCR-2 (OSM-9 and capsaicin receptor-related) is a TRPV (vanilloid subfamily of transient receptor potential channel) protein that regulates serotonin (5-HT) biosynthesis in chemosensory neurons and also mediates olfactory and osmotic sensation file:worm/ocr-2/ocr-2-deep-research-falcon.md OCR-2 mediates olfactory and osmotic sensation through different molecular determinants |
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Download this section (compressed HTML)Q: What is the precise ionic selectivity of the OCR-2/OSM-9 heteromeric channel?
Q: How does OCR-2 contribute to the non-cell autonomous UPR signaling in sensory neurons?
Q: What is the stoichiometry of the OCR-2/OSM-9 heteromeric channel?
Q: Are there other OCR family members that can substitute for OCR-2 in different neurons?
Q: How does the N-terminal domain of OCR-2 specifically regulate osmosensation vs olfaction?
Experiment: Single-channel patch clamp recording to determine the conductance and selectivity of OCR-2/OSM-9 channels
Hypothesis: The OCR-2/OSM-9 heteromeric channel has specific ionic conductance and selectivity properties
Type: electrophysiology
Experiment: Cryo-EM structure determination of the OCR-2/OSM-9 heteromeric complex
Hypothesis: The heteromeric structure reveals the basis for cooperative channel function
Type: structural biology
Experiment: FRET or proximity ligation assays to confirm heteromeric assembly in native neurons
Hypothesis: OCR-2 and OSM-9 directly interact in sensory cilia
Type: microscopy
Experiment: Optogenetic activation experiments to distinguish OCR-2/OSM-9-dependent from independent pathways in ADL
Hypothesis: There are redundant temperature-sensing pathways in ADL neurons
Type: optogenetics
Experiment: Systematic domain swap experiments between OCR family members to map functional determinants
Hypothesis: Specific domains confer sensory modality specificity
Type: molecular genetics
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