WormAtlas-Neurotransmitter and Neuropeptide Receptors in C. elegans by Z. F. Altun
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Homolog/ OrthologC. elegans geneSequence nameTypeLigandExpression pattern*PropertiesOther notesReferences**
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NEUROTRANSMITTER RECEPTORS
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SEROTONIN (5HT)
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Receptors
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5-HT2ser-1 (5-HTCeL, 5-HTCeS)F59C12.2G protein-coupled receptor (GPCR) (Gαq); 7-transmembrane (7TM); coupled to Ca++ signalingSerotonin (a-methyl 5-HT for SER-1)RIA, RIC, URY (inconsistent), head, tail, ventral cord motor neurons, pharyngeal muscles (pm3, pm4, pm5, pm6, pm7, pm8), vulval muscle (variable expression depending on construct), PVT, PVQ, other tail neurons and some ray neurons, diagonal muscles of male, VNC motor neurons (not VCs), ray neurons, uterine cells, posterior intestineMetabotropic 5-HT receptor. SER-1 has low affinity for 5-HT, and a mixture of pharmacological similarities to mammalian 5-HT1 and 5-HT2 receptorsSER-1 is stimulated by alpha-methyl-5-HT, and probably antagonized by methiotheptin. SER-1 is required in both vulval muscle and neurons for the stimulation of egg-laying by 5-HT, but is completely dispensable for stimulation by the uptake inhibitor fluoxetine, and mostly dispensable for stimulation by the tricyclic antidepressant imipramine; SER-1 and SER-7 are redundantly required for normal egg-laying. SER-1 is required for normal turning during male mating (ser-1 mutants show reduced male tail curling in exogenous 5-HT, but retain mating ability in the laboratory). SER-1 is weakly required for pharyngeal pumping. Stimulation of heterologously expressed SER-1 induces a rise in free intracellular calcium. Komuniecki et al, 2004; Carnell et al, 2005; Xiao et al 2006; Chase and Koelle 2007; Hapiak et al, 2009
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5-HT1ser-4, (cer-1, 5HT-Ce)Y22D7AR.137TM GPCR (Gαi/o); attenuates adenylyl cyclase activitySerotoninRIB and RIS, other head, pharyngeal neurons, sublateral neurons, retrovesicular ganglion neurons, PVT, and either DVA or DVCMetabotropic 5-HT receptor. Low affinity for 5-HT, overall has 5-HT1 propertiesHeterologously expressed SER-4 diminishes intracellular adenylate cyclase activity in response to 5-HT. SER-4 is required for normal inhibition of movement by 5-HT (ser-4 mutants are hyperactive). It is partly required for male tail curling (ser-4 mutants show reduced curling in exogenous 5-HT), but is dispensable for the stimulation of egg-laying by 5-HT and by the uptake inhibitor fluoxetine. SER-4 may actually inhibit egg-laying, since egg-laying ser-4 mutants are moderately hypersensitive to 5-HT, and mutant ser-4 hermaphrodites are partly depleted of eggs, suggesting that their egg-laying is weakly constitutive; however, SER-4 is required for stimulation of egg-laying by the tricyclic antidepressant imipramine.Olde and McCombie 1997;Tsalik et al, 2003; Dempsey et al, 2005; Carre-Pierrat et al, 2006
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5-HT6ser-5F16D3.77TM GPCR; independent of adenylyl cyclase activitySerotoninASH, AWB, head and tail neurons, vulval muscle, body wall muscle, intestineMetabotropic 5-HT receptor.SER-5 functions in the ASH chemosensory neurons to coordinate sensory input and locomotory behavior and in muscles to regulate the effects of 5-HT on egg laying; heterologously expressed ser-5 has no effect on adenylate cyclase signalingCarre-Pierrat et al, 2006; Harris et al, 2009
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5-HT7ser-7C09B7.17TM GPCR (Gαs); activates adenylyl cyclase activitySerotoninHead and tail neurons, pharyngeal neurons (I2, I3, I4, I6, M2, M3, M4, M5, MC), vulval muscles, and intestineHigh affinity for 5-HT and tryptamine, but not for 5-CT (5-Carboxamidotryptamine). Heterologously expressed ser-7 stimulates intracellular adenylate cyclase activity in response to 5-HT. SER-7 is required for stimulation of egg-laying or pharyngeal pumping by 5-HT, for regular pumping in response to bacteria, and probably also for 5-HT to activate MC neurons; SER-7 and SER-1 are redundantly required for normal egg-laying.Hobson et al, 2003 and 2006
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?mod-1K06C4.65-HT-gated chloride channelSerotoninAIA, AIB, AIY, AIZ, RIC, RID, RIM and other head neurons, VNC neurons, tail neurons, not in muscle cellsMOD-1 channel and the SER-6 GPCR play specific roles in 5-HT-induced fat reduction and they define distinct mechanisms mediating serotonergic fat regulation. mod-1 ; ser-6 double mutants have higher fat levels than the single mutants.Ranganathan et al, 2000; Wenick and Hobert, 2004; Srinavasan et al, 2008; Luedtke et al, 2010, Li et al, 2012
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lgc-50T20B12.9Ligand-gated ion channel (mod-1 group)Jones and Sattelle, 2008
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Homolog/OrthologC. elegans geneSequence nameTypeLigandExpression patternPropertiesOther notesReferences
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DOPAMINE (DA)McDonald et al, 2006
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Receptors
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D1-likedop-1F15A8.57TM GPCR (Gαs)DopamineALM, ALN, AUA, AVM, PHC, PLM, PLN, PVQ, PVD, RIB, RIM, RIS, some unidentified neurons in the head, cholinergic VNC motor neurons, interneurons, excretory gland cells, head muscles, and sensory neuronal support cells When coexpressed with bovine or C. elegans Gas, DOP-1 stimulates potassium channel activity.DOP-1 is required cell autonomously in the touch neurons for modulation of mechanosensory behaviors such as tap habituation. It is required for regulation of locomotion via antagonism of the DOP-3 in cholinergic neurons. RNAi leads to slower anterior movement, poor reversals and poor touch response. DOP-3 and DOP-1 probably counter one another through the GOA-1/Galpha(o) and EGL-30/Galpha(q) signaling pathwaysTsalik et al, 2003; Sanyal et al, 2004
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D2-likedop-2 (dop-2L)K09G1.47TM GPCR (Gαi/o)DopamineADE, CEP, PDA, PDE, RIA, RID, SIA, SIB, unidentified neurons in the head, male raySuo et al, 2003 and 2004; Tsalik et al, 2003
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D2-likedop-3T14E8.37TM GPCR DopamineASE, PVD, RIC, SIA, other head and tail neurons, cholinergic (weak) and GABAergic (strong) VNC motor neurons, bodywall musclesRequired for the normal slowing of locomotion by well-fed animals moving onto a bacterial lawn ('basal slowing'), but not for the enhanced slowing of starved animals ('enhanced slowing response'); DOP-3 is also required for the paralysis of animals by excess dopamine, with dop-3 mutants showing significant resistance to such paralysis; DOP-3 is antagonized by DOP-1 (since a dop-1 mutation suppresses the dop-3 slowing and paralysis mutant phenotypes). DOP-3 and DOP-1 probably counter one another through the GOA-1/Ga(o) and EGL-30/Ga(q) signaling pathways. DOP-3 and DOP-1 are coexpressed in cholinergic motor neurons and PVD mechanosensory neurons, and exert their antagonistic effects in the former. dop-3 mutants share a dopamine-resistant phenotype with goa-1, dgk-1, eat-16 and gpb-2 mutantsChase et al, 2004; Chase and Koelle 2007; Suo et al, 2009
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Human TAR vs D1-likedop-4C52B11.37TM GPCR (Gα?)DopamineASG, AVL, CAN, I1, I2, PQR, other head neurons (weak and variable expression), ASH, male ray 8, vulval cells, intestine, rectal gland, rectal epitheliumFood acutely enhances ASH-mediated aversive responses (eg to copper or glycerol) via dopaminergic signaling; bacteria are sensed by the mechanosensory CEP neurons that release DA to enhance somatic calcium transients in ASH via DOP-4 receptor, and increase ASH-driven avoidance behavior
Komuniecki et al, 2004; Sugiura et al, 2005, Ezcurra et al., 2011; Sengupta, 2013
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Homolog of human melatonin type 1b receptors, and more generally of mammalian dopamine and serotonin (5-HT) receptorsdop-5T02E9.37TM GPCR (Gα?)Dopamine? Serotonin?ASE, other head and tail neuronsRequired for full sensitivity to 5-HT, normal brood sizes and pharyngeal pumping, partly required for male tail curlingKomuniecki et al, 2004; Carre-Pierrat et al, 2006
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D2 or D3 dopamine receptors (mammalian homolog)dop-6C24A8.17TM GPCR (Gα?)DopamineHead neurons; unidentified cells in tailDOP-6 might act redundantly with DOP-2 to promote the basal slowing response to bacterial feeding, or it might account for the residual response to excess dopamine seen in triple dop-1/-2/-3 mutant. DOP-6 otherwise has no obvious function in RNAi assays of brood size, egg laying, pharyngeal pumping, locomotion, or male matingKeating et al, 2003; Komuniecki et al, 2004; Carre-Pierrat et al, 2006
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Ligand unspecified
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C24A8.6C24A8.6GPCR for small molecule neurotransmitters. 7TM rhodopsin family. Closest to C24A8.1 in phylogenetic tree?Keating et al, 2003
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Homolog/ OrthologC. elegans geneSequence nameTypeLigandExpression patternPropertiesOther notesReferences
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OCTOPAMINE (OA)
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Receptors
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octr-1F14D12.67TM GPCR (Gαs?)OctopamineExclusively in a subset of head and tail neurons, ASHOctopaminergic inhibition of ASH-mediated aversive responses is mediated by three different octopamine receptors; OCTR-1 , SER-6 and SER-3. OCTR-1 and SER-3 antagonistically modulate ASH signaling directly, while SER-6 activates peptidergic signaling cascades by stimulating the release of inhibitory neuropeptides. OCTR-1 acts in ASH and ASI to actively suppress innate immune responses by down-regulating the expression of noncanonical unfolded protein response genes in nonneuronal tissues.





Chase and Koelle, 2007; Komuniecki et al, 2004; Wragg et al, 2007; Mills et al., 2012
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5HT4ser-3K02F2.67TM GPCR (Gαq/Gαs?)Octopamine/serotonin?Pharynx, head (including SIA, ASH) and tail (PHA, PHB, PVQ) neurons, head muscles, phasmid sockets, nerve ring, and intestine, spermatheca, eggs, gonad, vulva.Mixed 5HT1 and 5HT2 properties, low affinity for 5HT, alpha-methyl 5HT as an agonist, mianserin as an agonist. SER-3 activity is required for normally high brood sizes and for embryonic development, and weakly required for pharyngeal pumping.SER-3 is required in the SIA neurons for response to the absence of food and to exogenous octopamine. Along with SER-4, SER-3 mediates the dietary restriction-based lifespan-extending effects of mianserin, in C. elegans; when expressed in HEK293 cells, ser-3 mediates a response to octopamine and to tyramine, but not serotonin. SER-3 is required for normal inhibition of movement by 5-HT, with ser-3 mutants being hyperactive and excessively curling their male tails. SER-3 activity is also required for normally high brood sizes and for embryonic development, and weakly required for pharyngeal pumping. Octopaminergic inhibition of ASH-mediated aversive responses is mediated by three different octopamine receptors; OCTR-1 , SER-6 and SER-3. OCTR-1 and SER-3 antagonistically modulate ASH signaling directly, while SER-6 activates inhibitory peptidergic signaling cascades by stimulating the release of an array of neuropeptides.Carre-Pierrat et al, 2006; Suo et al, 2006; Mills et al., 2012
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ser-6Y54G2A.357TM GPCR (Gαq)OctopamineHead neurons, including the AWB, ADL and ASI sensory neurons, posterior ventral cord motor neurons and the intestine.Couples to Gαq in Xenopus oocytes.SER-6 functions as part of a signaling pathway that mediates serotonin-induced fat reduction via transcriptional regulation of lipid oxidation genes. mod-1 and peripherally expressed metabolic genes define a pathway of serotonergic fat regulation that is mechanistically distinct from that defined by ser-6. Octopaminergic inhibition of ASH-mediated aversive responses is mediated by three different octopamine receptors , OCTR-1 , SER-6 and SER-3. The activation of SER-6 in the AWB, ADL and ASI sensory neurons stimulates the release of a large and diverse group of peptides that ultimately inhibit ASH-mediated aversive responses.



Komuniecki R, pers. comm.; Mills et al., 2012; Srinavasan et al, 2008
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Homolog/ OrthologC. elegans geneSequence nameTypeLigandExpression patternPropertiesOther notesReferences
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TYRAMINE (TA)Branicky and Schafer, 2009
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Receptors
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ser-2C02D4.27TM GPCR (Gαi/o)TyramineSome pharyngeal cells, head mucles. ser-2A: AIY, ALN, AUA, AVH, CAN, DA9, LUA, NSM, PVC, RIA, RIC, RID, SABD, SABV, SDQ, head muscles, diagonal muscles, pm1/6 muscles. ser-2B: AIY, AIZ, BDU, DVA, PVT, RID, RME, SIAD, SIAV, excretory gland. ser-2d: OLL and PVD. ser-2: AIY, AVH, AIZ, ALN, BDU, PDA, RIA, RIC, RID, RME, ut1, ut2Encodes at least four tyramine 7 TM domain receptors (GPCRs), by alternative splicing from three different promoters, that have distinct but partially overlapping expression patternsThe deletion ser-2(pk1397) mutant has no obvious phenotypeRex and Komuniecki 2002; Tsalik et al, 2003; Komuniecki et al, 2004
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5HT5tyra-2F01E11.57TM GPCR (Gαi/o vs Gα?)TyramineMC and NSM pharyngeal neurons, the AS family of amphid neurons (ASE, ASG, ASH, ASI) and neurons in the nerve ring, body and tail including PVD, CAN and the ALMKomuniecki et al, 2004; Rex et al, 2005
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tyra-3M03F4.37TM GPCR (Gαq); independent of adenylyl cyclase activityTyramine OctopamineCEP, ADE, tail neurons, and vulvaTYRA-3 acts in sensory neurons that detect environmental cues, suggesting that the internal catecholamines detected by TYRA-3 regulate responses to external conditions. Natural variation in TYRA-3 affects food patch leaving, a behaviour representative of the exploration–exploitation decision (i.e., the time at which animals choose to abandon a depleting food supply to restart foraging). Tyramine and octopamine independently inhibit serotonin-stimulated aversive behaviors through TYRA-3 and OCTR-1, respectively. TYRA-3 is required for normal inhibition of movement by 5-HT, with tyra-3(RNAi) animals being hyperactive. Chase et al, 2004; Carre-Pierrat et al, 2006; Wragg et al, 2007, Bendesky et al., 2011
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lgc-55Y113G7A.5Ligand-gated ion (chloride) channel Tyramine?ALN, AVB, HSN, IL1D, IL1V, RMD, SMDD, SMDV, SDQ, uv1, neck muscles, tail muscleTouch to the anterior of the animal activates the AVA backward locomotion command interneuron, which in turn activates the tyraminergic RIM mototr neuron. Tyramine release from the RIM neurons activates the tyramine-gated chloride channel LGC-55, which is expressed in the forward locomotion command interneuron AVB and cells of the head movement circuit; RMD. SMD, and neck muscles. Activation of LGC-55 causes hyperpolarization of neck muscles and the AVB neuron inducing the suppression of head movements and sustained backward locomotion in response to anterior touch.Pirri et al, 2009; Pirri and Alkema, 2011
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Homolog/ OrthologC. elegans geneSequence nameTypeLigandExpression patternPropertiesOther notesReferences
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TRACE AMINESBranicky and Schafer, 2009
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Candidate GPCRs predicted to bind either small-molecule neurotransmitters (trace amine-associated (TAA) receptors) or neuropeptides
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F59D12.1F59D12.1GPCR. 7TM rhodopsin family. GPCR for small molecule neurotransmitters. Closest to T02E9.3 in phylogenetic tree.Melatonin?
Animals look slow and paralyzed with RNAi against F59D12.1. Exogenously applied melatonin decreases locomotion rates in 15 min treatments, suggesting that melatonin directly regulates neural activities for locomotion. This melatonin signaling functions through MT1-like melatonin receptors, because the MT1\/2 receptor antagonist luzindole effectively blocked the effect of melatonin on locomotion, while MT2-specific antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT) and MT3-selective antagonist prazosin had no effect. Alternatively, long-term treatment with prazosin specifically altered homeostatic states of the worm, suggesting another melatonin-signaling pathway through MT3-like receptors Keating et al, 2003; Tanaka et al, 2007
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T21B4.4T21B4.4GPCR. 7TM rhodopsin family. GPCR for small molecule neurotransmitters. Closest to F42D1.3 in phylogenetic tree. Serpentine receptor class sx (Srsx)?
Keating et al, 2003
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Homolog/ OrthologC. elegans geneSequence nameTypeLigandExpression patternPropertiesOther notesReferences
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ACETYLCHOLINE
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Receptors
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gar-1 (acm-1)C15B12.5Muscarinic. GPCRAchSome head neurons with ciliated endings and in PVM neuron. Three PCR products of expected sizes found at all developmental stages.Although gar-1 is most closely related to muscarinic acetylcholine receptors (mAChR), it is pharmacologically distinct from them in its response to certain ligands; e.g. oxotremorine, atropine, scopolamine and pirenzepine do not work on GAR-1 and GAR-2 as effectively as they do on GAR-3. Electrophysiological studies indicate that gar-1 couples to the inhibitory subunit of G proteins (Gi) and not to Gs or to Go/Gq.RNAi leads to sluggish animalsLee et al, 2000; Park et al, 2000; Keating et al, 2003
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gar-2 (formerly acm-2)F47D12.1Muscarinic. GPCRAChAIY, Ciliated head neurons, ventral cord motor neurons, and HSN. From mid-embryogenesis through adulthood.When expressed in Xenopus oocytes treated with acetylcholine, gar-2 is able to activate a mammalian G protein-activated inwardly rectifying K+ (GIRK1) channel, but not other channels, suggesting that GAR-2 couples to G proteins of the Gi family. Pharmacological analyses indicate that GAR-2 exhibits properties distinct from mammalian muscarinic AChRs; GAR-2 is not inhibited by muscarinic antagonists (atropine , scopolamine, and pirenzepine), and muscarinic ligands (such as oxotremorine, atropine, scopolamine and pirenzepine) do not work on GAR-1 and GAR-2 as effectively as they do on GAR-3.Lee et al, 2000; Park et al, 2000; Wenick and Hobert, 2004
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gar-3 (aka acm-3)Y40H4A.1Muscarinic. GPCRAChPharyngeal muscle, I3, in neurons of the extrapharyngeal nervous system, anal depressor muscle, VD and DD ventral cord neurons, some tail and nerve ring neurons, and body wall muscles. Male-specific SPC motor neurons, PCB and PCA postcloacal sensilla neurons and male spicule protractor musclesGAR-3 appears most similar to mammalian muscarinic ACh receptors (mAChRs), among the three G-protein-linked ACh receptors. Required for regulation of membrane potential and excitation-contraction coupling in pharyngeal muscle and thus, for normal feeding behavior. GAR-3 likely acts upstream of GPB-2, a G-protein beta-subunit in regulation of pharyngeal pumpingHwang et al, 1999; Park et al, 2003; Steger and Avery, 2004; Liu et al, 2007; Rand, 2007
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unc-29 grouplev-1 (aka acr-1 and tmr-1)F09E8.7nAChR (nicotinic acetylcholine receptor). Ligand-gated cation (Ca++/Na+) channel. unc-29 group; non-alpha subunit.AChAll body wall muscle cells and a subset of ventral cord motor neuronsnAChRs are pentameric membrane proteins that are ligand-gated cation channels and mediate fast synaptic transmission at neuromuscular junctions and in the nervous system. Subunits of nAChRs fall into two main categories: alpha subunits are defined by adjacent cysteines which contribute to the ACh binding site, while non-alpha subunits lack this motif. LEV-1, a non-alpha subunit, forms a ligand (levamisole)-gated cation channel when coexpressed with UNC-29 (non-alpha subunit) and UNC-38 (alpha subunit) or UNC-63 (alpha subunit).LEV-1 is required for normal locomotion, regulation of egg-laying behavior. When mutated, lev-1 confers resistance to levamisole.Culetto et al, 2004;Gottschalk et al, 2005; Jones et al, 2007
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unc-29 (aka unc-21 and unc-56 and tmr-4)T08G11.5nAChR. unc-29 group; non-alpha subunitAChBody muscles, the ventral and dorsal cords and in the nerve ring where head muscles are innervatedForms a ligand-gated cation channel when coexpressed with LEV-1 (non-alpha subunit) and UNC-38 (alpha subunit) or UNC-63 (alpha subunit).UNC-29 is required for normal locomotion and egg-layingFleming et al, 1997; Gottschalk et al, 2005
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acr-2K11G12.2nAChR. unc-29 group; non-alpha subunitAChDA, DB, IL1, PVQ, RMD, VA and VBForms a ligand-gated cation channel when coexpressed with the unc-38 (alpha) subunitSquire et al, 1995; Rand, 2007
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acr-3K11G12.7nAChR. unc-29 group; non-alpha subunitAChUnknownForms a ligand-gated cation channel when coexpressed with UNC-38 (alpha) subunit
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unc-38 groupunc-38F21F3.5nAChR. unc-38 group; alpha subunitAchVentral and dorsal nerve cords, many neurons, body wall muscles, vulval and (male) sex muscles, including the protractor muscles. UNC-38 is expressed postsynaptically in muscles and neurons where it colocalizes with TAX-6, and with ACR-8, ACR-12, and UNC-29, respectivelyForms a ligand-gated cation channel when coexpressed with ACR-2, ACR-3, UNC-29, and LEV-1 (non-alpha nAChR subunits)Required for normal locomotion and egg-laying, and functions as a subunit of a ligand-gated cation channel that likely mediates fast actions of acetylcholine at neuromuscular junctions and in the nervous system. ACR-12 colocalizes with some, but not all, UNC-38-containing postsynaptic receptor clusters, suggesting that ACR-12 contributes to only a subset of these receptor clusters Baylis et al, 1997; Mongan et al, 2002; Schafer, 2002; Gottschalk et al, 2005
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acr-6ZK973.5nAChR. unc-38 group; alpha subunitAchPredicted to function in regulation of fast neurotransmission
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unc-63 (aka lev-7 and tmr-3)Y110A7A.3nAChR. unc-38 group; alpha subunitAchBody wall muscles, vulval muscles, and a large number of neurons including motor neurons in the ventral nerve cord (AS, DA, DB, VB, VD, VC) and neurons in the head, posterior lateral, preanal, and lumbar ganglia. No expression is observed either in the sphincter muscle or in the anal depressor muscle. Forms a ligand-gated cation channel when coexpressed with UNC-29 and LEV-1 (non-alpha nAChR subunits)Required for normal locomotion and regulation of egg-laying behavior Mongan et al, 2002; Culetto et al, 2004; Schafer, 2002
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acr-16 groupacr-7T09A5.3nAChR. acr-16 group; alpha subunitAchPharyngeal muscle and in tail neurons distal to the anusEncodes an alpha-7-like homomer-forming subunit of the nicotinic acetylcholine receptor (nAChR) superfamily
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acr-9C40C9.2nAChR. acr-16 group; non-alpha subunit AchUnknown
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acr-10R02E12.8nAChR. acr-16 group; alpha subunitAchUnknownEncodes an alpha-7-like homomer-forming subunit of the nicotinic acetylcholine receptor (nAChR) superfamily
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acr-11D2092.3nAChR. acr-16 group; alpha subunitAchUnknown
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acr-14T05C12.2nAChR. acr-16 group; non-alpha subunitAchAIY, other head neurons, AS, DA, DB, DD, HSN, VB, VC4, VC5, muscle, intestine Fox et al, 2005; von Stetina et al, 2007; Rand, 2007
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acr-15F25G6.4nAChR. acr-16 group; alpha subunitAchAVA, AVB, DVA, I5, RID, RIM, PVQ, SAA, SIA, SIB, SMB (?), SMD, all ventral cord motor neurons except DD, some unidentified neurons in the head. Also expressed in head muscles (weak), body wall muscles (weak). Feng et al, 2006; von Stetina et al, 2007
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Orthologous to human nicotinic cholinergic receptor alpha 7acr-16F25G6.3nAChR. acr-16 group;alpha subunit AchSubset of neurons; AVA, RIB, RID, SIB, SMD, CEP(?), ADE(?), DB motor neurons and some unidentified neurons in the head and tail. Also expressed in anal depressor, head muscles (strong), body wall muscles (strong; localizes to the tips of muscle arms, specific regions of the muscle cell membrane that form synapses with neuronal processes), but not vulval muscles ACR-16 functions as a ligand-gated ion channel that is required for the major fast cholinergic excitatory current at C. elegans neuromuscular junctions. When expressed in Xenopus ooctyes, ACR-16 is active as a homomeric receptor and responds robustly to acetylcholineFrancis et al, 2005; Touroutine et al, 2005; Feng et al, 2006
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acr-19C31H5.3nAChR. acr-16 group; alpha subunitAchUnknown
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acr-21F27B3.2nAChR. acr-16 group; alpha subunitAchUnknownACR-21 is a highly divergent member of the 'ACR-16' class of nAChR subunits
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acr-25Y73B6BL.42nAChR. acr-16 group; non-alpha subunitAchUnknownJones and Sattelle, 2004; Jones et al, 2007
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eat-2Y48B6A.4nAChR. acr-16 group; non-alpha subunit Achpm4 and pm5. EAT-2::GFP fusion protein is localized to small dots near the junction of pharyngeal muscles pm4 and pm5Ligand-gated ion channel subunit most closely related to the non-alpha-subunits of nicotinic acetylcholine receptors (nAChR)Functions postsynaptically in pharyngeal muscle to regulate the rate of pharyngeal pumping; EAT-2 is also required for normal life span and defecation; a functional EAT-2::GFP fusion protein localizes to two small dots near the junction of pharyngeal muscles pm4 and pm5, which is the site of the posteriormost MC motor neuron processes and the MC synapse; eat-2 genetically interacts with eat-18, which encodes a predicted transmembrane protein expressed in pharyngeal muscle and required for proper function of pharyngeal nicotonic receptors.McKay et al, 2004
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acr-8 group (nematode-specific)acr-8ZC504.2nAChR. acr-8 group; alpha subunitAchAll bodywall muscles, anal and vulval muscles, ventral cord motor neurons (punctate sites along nerve cords), head neurons and nerve ring processes, and in tail neurons
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acr-12R01E6.4nAChR. acr-8 group; alpha subunitAchVentral cord motor neurons, multiple neurons in the head, and tail neurons (exclusively in neurons)ACR-12 is predicted to mediate fast excitatory neurotransmission, however loss of acr-12 activity via mutation or RNAi results in no obvious defects. ACR-12 copurifies with UNC-29 and LEV-1, suggesting that ACR-12 can form receptors with these two non-alpha AChR subunits. ACR-12 colocalizes with some, but not all, UNC-38-containing postsynaptic receptor clusters, suggesting that ACR-12 contributes to only a subset of these receptor clustersGottschalk et al, 2005
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acr-13 (lev-8)C35C5.5nAChR. acr-8 group; alpha subunitAchExpression of a LEV-8::GFP reporter construct begins at the L1 larval stage. Expression is detected in body wall muscles, uv1 and uv2 uterine muscles, anal depressor muscle, and neurons, including PVT, ALA, many ventral cord neurons, including all DD cells, many head neurons, IL and OL socket cells Required for normal rates of pharyngeal pumping and for fully wild-type responses (increased egg laying and body wall muscle contraction) to the nAChR agonist and antihelmintic levamisoleTowers et al, 2005; Gottschalk et al, 2005
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deg-3 group (nematode-specific)deg-3K03B8.9nAChR. deg-3 group; alpha subunitAChConsistent with their role in metabolite chemosensation, DEG-3 and DES-2 are expressed in nonsynaptic regions such as the sensory endings of the IL2 chemosensory neurons; DEG-3 and DES-2 are also detected in the touch cell neurons (ALM, AVM, PLM), anterior head muscles, AVG, PVD, PVC, FLPDEG-3 can form heteromeric channels with a second alpha subunit, DES-2, and in vivo these channels appear to be required for chemosensation of choline; deg-3 and des-2 reside in an operon, and consistent with their role in metabolite chemosensation, are expressed in nonsynaptic regions such as the sensory endings of the IL2 chemosensory neurons Originally defined by a gain-of-function mutation that results in neuronal degeneration and uncoordinated movementTreinin et al, 1998; Yassin et al, 2001
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acr-4 (des-2)T26H10.1nAChR. deg-3 group; alpha subunitAchConsistent with their role in metabolite chemosensation, DEG-3 and DES-2 are expressed in nonsynaptic regions such as the sensory endings of the IL2 chemosensory neurons; DEG-3 and DES-2 are also detected in the touch cell neurons (ALM, AVM, PLM), anterior head muscles, AVG, PVD, PVC, FLP. Also expressed in ALADEG-3 can form heteromeric channels with a second alpha subunit, DES-2, and in vivo these channels appear to be required for chemosensation of choline; deg-3 and des-2 reside in an operon, and consistent with their role in metabolite chemosensation, are expressed in nonsynaptic regions such as the sensory endings of the IL2 chemosensory neuronsTreinin et al, 1998; van Buskirk and Sternberg, 2010
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acr-5K03F8.2nAChR. deg-3 group; alpha subunitAchExpressed exclusively in the nervous system. Expression is initiated in the embryo and persists throughout adult life. Expressed in DB, VB neurons and unidentified neurons in the head and tail .Winnier et al, 1999
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acr-17F53E10.2nAChR. deg-3 group; alpha subunit AChUnknownMongan et al, 2002; Sattelle et al, 2002; Schafer, 2002
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acr-18F28F8.1nAChR. deg-3 group; alpha subunitAChUnknownMongan et al, 2002; Sattelle et al, 2002; Schafer, 2002
72
acr-20R06A4.10nAChR. deg-3 group; alpha subunitAChUnknown
73
acr-23F59B1.9nAChR. deg-3 group; alpha subunitAChUnknown
74
acr-24Y73F8A.30nAChR. deg-3 group; alpha subunitAchUnknownJones and Sattelle, 2004; Jones et al, 2007
75
Ungroupedlgc-11 (acr-22)F48E3.7Ligand-gated ion channel of the cys-loop superfamily with sequence similarity to nicotinic acetylcholine receptor subunits, including the vertebrate neuronal acetylcholine receptor alpha-9 subunitsAchUnknown.Mongan et al, 2002; Jones et al, 2007; Jones and Sattelle, 2008
76
acc-1F58G6.4Acetylcholine-gated chloride channel (not found in vertebrates)AchUnknownPutrenko et al, 2005
77
acc-2C53D6.3Acetylcholine-gated chloride channel (not found in vertebrates)AchUnknownPutrenko et al, 2005
78
acc-3F55D10.5Acetylcholine-gated chloride channel (not found in vertebrates)AchUnknownPutrenko et al, 2005
79
acc-4T27E9.9Acetylcholine-gated chloride channel (not found in vertebrates)AchUnknownPutrenko et al, 2005
80
lgc-46Y71D11A.5Ligand-gated ion channel (acc-1 group)Jones and Sattelle, 2008
81
lgc-47F47A4.1Ligand-gated ion channel (acc-1 group)Jones and Sattelle, 2008
82
lgc-48C50B6.11Ligand-gated ion channel (acc-1 group)Jones and Sattelle, 2008
83
lgc-49K10D6.1Ligand-gated ion channel (acc-1 group)Jones and Sattelle, 2008
84
cup-4C02C2.3Non-alpha ligand-gated ion channel with similarity to the nicotinic acetylcholine receptorsAch ?Coelomocytes. Localizes primarily to vesicles scattered around the cytoplasm. While some of the CUP-4::GFP localized around the nucleus, presumably in the endoplasmic reticulum (ER) membrane, the general pattern of localization of CUP-4::GFP was quite distinct from that of cytochrome b5, a marker for smooth ER, and from TRAM, a marker for the rough ER.hese results are consistent with CUP-4::GFP localizing at steady state to the Golgi apparatus or to the plasma membrane/endosomes.Required cell autonomously for efficient fluid endocytosis in coelomocytes; cup-4 mutant animals display reduced levels of plasma membrane phosphatidylinositol 4,5-bisphosphate, suggesting that CUP-4 may regulate endocytosis via regulation of phospholipase C activity; in addition, cup-4 mutants display disorganized clathrin and RME-1 at the coelomocyte plasma membraneFares and Greenwald, 2001; Jones and Sattelle, 2004; Patton et al, 2005
85
lgc-31F21A3.7nAChR? Ligand-gated ion channelAch ?Jones and Satelle, 2008
86
Homolog/ OrthologC. elegans geneSequence nameTypeLigandExpression patternPropertiesOther notesReferences
87
GABA (gamma-aminobutyric acid )
88
Receptors
89
GABA-ARunc-49T21C12.1Ligand-gated anion (chloride) channelGABADorsal and ventral head and body wall muscles on both the dorsal and ventral sides (localized in postsynaptic terminals at the NMJs). Isoform-specific expression also seen in the anal sphincter muscle (unc-49B::gfp but not unc-49C::gfp animals). Variable, weak fluorescence in head gangliaEncodes multiple subunits of a heteromeric GABA receptor. There are 9 cDNA-confirmed or partially-confirmed isoforms (T21C12.1a-T21C12.1i). UNC-49 activity is required for postsynaptic GABA responsiveness, and thus, for normal regulation of locomotionBamber et al, 1999; Jorgensen, 2005; Jones et al, 2008
90
lgc-36F07B10.5Ligand-gated ion channel (unc-49 group)Jones and Satelle, 2008
91
Human gamma-aminobutyric acid A receptor gamma 2 (GABRG2)lgc-37ZC482.5Ligand-gated ion channel (unc-49 group)All of the touch receptor neurons (ALM, AVM, PLM), ventral cord motor neurons, and many neurons in the head and some in the tail.Jones and Satelle, 2008; Topalidou and Chalfie, 2011
92
lgc-38F11H8.2Ligand-gated chloride channelGABAAIYWenick & Hobert, 2004; Jones and Satelle, 2008
93
gab-1 (gbr-1)ZC482.1A GABA receptor beta-like subunit with both the neurotransmitter-gated ion-channel ligand binding and transmembrane domainsGABAAll touch receptor neurons (ALM, AVM, PLM), ventral cord motor neurons, and many neurons in the head and some in the tail.GAB-1 can form a GABA-responsive channel when co-expressed with alpha/gamma type subunits in a heterologous expression systemInvolved in the mechanism of resistance to the widely used broad-spectrum anthelmintic drug IvermectinFeng et al, 2002; Topalidou and Chalfie, 2011
94
ggr-1 (gbr-4)C09G5.1Ligand-gated chloride channel (a predicted member of the GABA/glycine receptor family of ligand-gated chloride channels)GABAAIB, AVH, PVR, PVQ, and SMDV neurons and in some motor neurons in the ventral cord, and in the egg-laying musclesAffects thermotaxis.
95
ggr-2 (gbr-5)C45B2.4Ligand-gated chloride channel (a predicted member of the GABA/glycine receptor family of ligand-gated chloride channels)GABACAN, DD, HSN, SIAV, SMDV, SMDD. Egg-laying muscles (weak)Affects thermotaxis.
96
ggr-3 (gbr-6)F09C12.1Ligand-gated chloride channel (a predicted member of the GABA/glycine receptor family of ligand-gated chloride channels)GABAAVA, AVB, DVA, SIAD, SMDD, and in some other neurons of the nerve ring
97
lgc-39F09G2.5Ligand-gated ion channel (ggr-1 group)Jones and Satelle, 2008
98
lgc-40T24D8.1Ligand-gated ion channel (ggr-1 group)Jones and Satelle, 2008
99
lgc-41C39B10.2Ligand-gated ion channel (ggr-1 group)Jones and Satelle, 2008
100
lgc-42Y39A3B.2Ligand-gated ion channel (ggr-1 group)Jones and Satelle, 2008
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