cGMP-dependent sensory transduction in Caenorhabditis elegans ciliated neurons

Many Caenorhabditis elegans sensory neurons turn an environmental stimulus into an electrical signal through the second messenger cGMP. A guanylyl cyclase in or near the sensory cilium makes cGMP. The cGMP then opens a cyclic nucleotide-gated (CNG) cation channel made of the pore-forming alpha subunit TAX-4 and the modulatory beta subunit TAX-2. The resulting cation and Ca2+ influx changes the activity of the neuron. The channel is the same in different neurons, but the cyclase differs with the stimulus. In the AWC olfactory neurons, odorant receptors act through the stimulatory Galpha ODR-3, and the transmembrane guanylyl cyclases ODR-1 and DAF-11 act downstream and are required for responses to AWC-sensed odors. In the AFD thermosensory neurons, the receptor guanylyl cyclases GCY-8, GCY-18 and GCY-23 sit in the microvilli of the sensory ending and together are required for temperature-evoked currents. GCY-8 is the one needed to carry out isothermal tracking, GCY-18 is the main cyclase at 20-25 C, and GCY-23 is modulatory; all three help set the temperature range of tracking. In the URX and BAG gas-sensing neurons, heme-containing soluble guanylyl cyclases are both the cyclase and the O2 sensor: GCY-35/GCY-36 respond to rises in O2 and GCY-31/GCY-33 to falls. tax-4 and tax-2 are expressed in the thermosensory, gustatory and olfactory neurons. tax-4 mutants fail to respond to temperature and to soluble or volatile attractants, and they are defective in oxygen responses. A separate set of C. elegans sensory neurons, including AWA and ASH, uses OSM-9/OCR-2 TRPV channels instead of this cGMP-CNG pathway.

Boundary. This is a concrete C. elegans module for the primary transduction step in ciliated sensory neurons that use cGMP. A guanylyl cyclase makes cGMP, and cGMP gates the TAX-4/TAX-2 CNG channel. The cyclase step is a variant set along the neuron and stimulus axis (AWC odors, AFD temperature, URX/BAG oxygen). In this concrete scope these variants coexist in one animal and are not alternatives, so the selection is ONE_OR_MORE. The CNG channel is a shared required part. Left out on purpose. (1) The OSM-9/OCR-2 TRPV branch, used in AWA olfaction and ASH nociception. It does not use cGMP and should get its own module. OCR-2 has a gene review but is therefore not a member here. OSM-9 does act in AWC, but as an adaptation factor and not as the transduction channel (PMID:12160748). (2) GPA-12. Its review places it in the epidermal antifungal G12/13-PKC-p38 pathway, not in sensory transduction. (3) Upstream receptors: AWC odorant GPCRs such as STR-2, and the photoreceptor LITE-1 in ASJ. They are described in text and not given annotons. The Galpha ODR-3 is the exception. It has a gene review and is modeled as the upstream G protein of the AWC cyclase step (PROVIDES_INPUT_FOR, because the sign of its effect on ODR-1/DAF-11 activity is not established). Other Galphas that act partly redundantly with ODR-3 in AWC, such as GPA-3, are not modeled. (4) Downstream modulators: EGL-4/PKG adaptation, TAX-6 calcineurin, the CNG-3 channel subunit and cGMP phosphodiesterases. (5) The ASE salt-sensing receptor guanylyl cyclases (GCY-22, GCY-5 and others). TAX-4/TAX-2 also act in ASE, but the cached primary evidence for ASE rGCs is abstract-only and indirect, so no ASE cyclase variant is modeled. (6) ASJ phototransduction, which also uses DAF-11, ODR-1 and TAX-2/TAX-4 (PMID:20436480). It is recorded here as context, not as a separate variant. Grounding. Every member has a gene review: ODR-3, ODR-1, DAF-11, GCY-8, GCY-18, GCY-23, GCY-35, GCY-36, GCY-31, GCY-33, TAX-4 and TAX-2. Each annoton uses the core molecular function and the processes and locations of that gene's review. All cyclases use guanylate cyclase activity (GO:0004383). The reviews of GCY-35, GCY-31 and GCY-33 also give oxygen sensor activity (GO:0019826) as a second core function, through the H-NOX heme. Because an annoton carries one function, the module keeps the cyclase activity that links these subunits to the CNG channel and records the O2 sensor activity in each annoton's notes. DAF-11 has no thermosensory role. Its review places it in AWC, AWB, ASI, ASJ and ASK chemosensation, ASJ phototransduction and dauer control. The AFD cyclases are located at the microvilli of the AFD sensory ending rather than in the cilium proper. The rGCs are written as parallel annotons in each variant. Whether they act as obligate heterodimers in vivo is not established for AWC or AFD. GCY-35 and GCY-36 are described as a complex, an alpha-like/beta-like sGC heterodimer (PMID:15203005, PMID:26791224), and the gcy-35 and gcy-36 reviews place both in the soluble guanylate cyclase complex (GO:0008074); the two annotons record this in their notes. The GCY-31/GCY-33 pairing rests on genetics and co-expression in BAG only (PMID:19323996), so no complex is asserted for it here or in the gcy-31 and gcy-33 core functions. The direction of the stimulus-evoked cGMP change differs between neurons and is not modeled. Relation to MODULE:nitric_oxide_cgmp_signaling. That module is the vertebrate-style NO-sGC-cGMP-PKG pathway. The worm GCY-35/GCY-36 and GCY-31/GCY-33 enzymes are atypical soluble guanylyl cyclases with heme H-NOX domains that sense O2. Their output here is the CNG channel, not PKG. The GO term nitric oxide-cGMP-mediated signaling (GO:0038060) is therefore not used. GO currently has no non-obsolete general "cGMP-mediated signaling" process term (GO:0019934 is obsolete), so the root concept uses the stimulus-detection process.