2021
The neural G protein Gαo tagged with GFP at an internal loop is functional in Caenorhabditis elegans
Kumar S, Olson AC, Koelle MR. The neural G protein Gαo tagged with GFP at an internal loop is functional in Caenorhabditis elegans. G3: Genes, Genomes, Genetics 2021, 11: jkab167. PMID: 34003969, PMCID: PMC8496287, DOI: 10.1093/g3journal/jkab167.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsGreen Fluorescent ProteinsGTP-Binding ProteinsSignal TransductionConceptsGreen fluorescent proteinCaenorhabditis elegansGenetic analysisHeterotrimeric G proteinsG protein GαoInternal loopC. elegansProtein complexesBiochemical purificationEpitope tagPlasma membraneAlpha subunitMolecular mechanismsFluorescent proteinGenetic studiesElegansGαoG proteinsEgg layingTransgenic expressionBiochemical studiesGαo proteinsBody morphologyProteinNeurotransmitter release
2020
Cellular Expression and Functional Roles of All 26 Neurotransmitter GPCRs in the C. elegans Egg-Laying Circuit
Fernandez RW, Wei K, Wang EY, Mikalauskaite D, Olson A, Pepper J, Christie N, Kim S, Weissenborn S, Sarov M, Koelle MR. Cellular Expression and Functional Roles of All 26 Neurotransmitter GPCRs in the C. elegans Egg-Laying Circuit. Journal Of Neuroscience 2020, 40: 7475-7488. PMID: 32847964, PMCID: PMC7511189, DOI: 10.1523/jneurosci.1357-20.2020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsEpithelial CellsNeural PathwaysNeuronsNeurotransmitter AgentsOvipositionReceptors, G-Protein-CoupledConceptsEgg-laying circuitNeurotransmitter GPCREgg-laying defectsModel organismsNeural circuitsExtrasynaptic signalsStandard laboratory conditionsSuch signalingGPCR expressionCell typesFunctional roleGPCRsNeurotransmitter signalsCellular expressionActivity of neuronsModel systemEpithelial cellsReceptor functionOrganismsNeurotransmitter receptorsLaboratory conditionsDistinct receptorsReceptor knockoutParkinson's diseaseCells
2018
Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans.
Koelle MR. Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans. WormBook 2018, 2018: 1-52. PMID: 26937633, PMCID: PMC5010795, DOI: 10.1895/wormbook.1.75.2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsHeterotrimeric GTP-Binding ProteinsNeurotransmitter AgentsSignal TransductionConceptsHeterotrimeric G proteinsC. elegansG proteinsRic-8 proteinsNew molecular componentsG protein signalingG alpha proteinsNeurotransmitter releaseGenetic screenMammalian orthologsSmall molecule neurotransmittersIndividual receptor typesProtein signalingReceptor homologG alphaElegansDistant cellsAlpha proteinAdditional GPCRsGenetic studiesIndividual neural circuitsGαMolecular componentsGαqGαo
2016
Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition
Collins KM, Bode A, Fernandez RW, Tanis JE, Brewer JC, Creamer MS, Koelle MR. Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition. ELife 2016, 5: e21126. PMID: 27849154, PMCID: PMC5142809, DOI: 10.7554/elife.21126.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsChloride ChannelsCholineFeedback, PhysiologicalFemaleGene Expression RegulationLocomotionMotor NeuronsMuscle ContractionOptogeneticsOvipositionPeriodicityReceptors, Biogenic AmineSerotoninSexual Behavior, AnimalSignal TransductionTyramineConceptsPassage of eggsUnderlying neural circuitsUv1 neuroendocrine cellsCommand neuronsMuscle contractionNeural circuitsNeuroendocrine cellsRhythmic activityBehavior circuitsCircuit activityCentral pattern generatorCircuit functionBody bendsFeedback inhibitionSlow locomotionPattern generatorNeuronsActivityVulva
2015
Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation
Coleman BD, Marivin A, Parag-Sharma K, DiGiacomo V, Kim S, Pepper JS, Casler J, Nguyen LT, Koelle MR, Garcia-Marcos M. Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation. Molecular Biology And Evolution 2015, 33: 820-837. PMID: 26659249, PMCID: PMC4760084, DOI: 10.1093/molbev/msv336.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsBiological EvolutionCaenorhabditis elegansCaenorhabditis elegans ProteinsEvolution, MolecularGene ExpressionGTP-Binding ProteinsGuanine Nucleotide Exchange FactorsModels, MolecularProtein BindingProtein ConformationProtein Interaction Domains and MotifsProtein MultimerizationReceptors, G-Protein-CoupledSignal TransductionConceptsGBA motifGEF activityG protein activationTrimeric G-protein signalingGuanine nucleotide exchange factor activityProtein activationG proteinsMammalian Gα subunitsG protein-mediated signalingMotif-containing proteinsGPCR-independent mechanismReceptor-independent G-protein activationExchange factor activityG protein signalingProtein-mediated signalingMammalian cell behaviorGOA-1Evolutionary conservationDivergent proteinsCaenorhabditis elegansBioinformatics searchGα subunitsMost invertebratesProtein signalingAccessory proteinsRNA ligation in neurons by RtcB inhibits axon regeneration
Kosmaczewski SG, Han SM, Han B, Meyer B, Baig HS, Athar W, Lin-Moore AT, Koelle MR, Hammarlund M. RNA ligation in neurons by RtcB inhibits axon regeneration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 8451-8456. PMID: 26100902, PMCID: PMC4500288, DOI: 10.1073/pnas.1502948112.Peer-Reviewed Original ResearchAn Evolutionarily Conserved Switch in Response to GABA Affects Development and Behavior of the Locomotor Circuit of Caenorhabditis elegans
Han B, Bellemer A, Koelle MR. An Evolutionarily Conserved Switch in Response to GABA Affects Development and Behavior of the Locomotor Circuit of Caenorhabditis elegans. Genetics 2015, 199: 1159-1172. PMID: 25644702, PMCID: PMC4391577, DOI: 10.1534/genetics.114.173963.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidRigorous genetic analysisBody wall musclesNeural circuit developmentCaenorhabditis elegansL1 animalsDevelopmental switchGenetic analysisGABAergic neuronsGABA responsesVertebrate brainMammalian neuronsStage animalsNeurotransmitter gamma-aminobutyric acidWall musclesChloride transportersMajor inhibitory neurotransmitterMuscle targetsTransporter 1Muscimol responsesGABA neuronsLocomotor circuitsExcitatory responsesCircuit developmentAgonist muscimol
2013
LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans
Li P, Collins KM, Koelle MR, Shen K. LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans. ELife 2013, 2: e00378. PMID: 23539368, PMCID: PMC3601818, DOI: 10.7554/elife.00378.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCaenorhabditis elegans ProteinsCalcium SignalingCell Adhesion MoleculesFemaleGenotypeIntracellular Signaling Peptides and ProteinsMorphogenesisMuscle ContractionMusclesMutationNeurogenesisOvipositionParacrine CommunicationPhenotypeReceptors, NotchSignal TransductionSodium ChannelsSynapsesVulvaConceptsPrecise synaptic connectivityNon-target musclesForm synapsesMADD-2Types of musclePresynaptic neuronsSynaptic targetsSynaptic connectivityCardinal featuresNervous systemGuidance moleculesTarget cellsLIN-12/NotchUNC-40/DCCMuscleCell typesArm extensionCellsMuscle armsEctopic expressionDiverse cell typesDCCArmExpressionNeurons
2012
Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans
Gürel G, Gustafson MA, Pepper JS, Horvitz HR, Koelle MR. Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans. Genetics 2012, 192: 1359-1371. PMID: 23023001, PMCID: PMC3512144, DOI: 10.1534/genetics.112.142125.Peer-Reviewed Original ResearchConceptsCaenorhabditis elegansLarge-scale genetic screensSer-4Direct postsynaptic targetsGenetic screenC. elegansSignaling proteinsGenetic systemNon-overlapping setsAdditional proteinsExtrasynaptic signalsMolecular mechanismsElegansSerotonin responseGenesRelease sitesMod 1Multiple receptorsProteinSerotonin controlSerotonergic neuronsPostsynaptic targetsSerotonin functionReceptorsSerotonin receptors
2011
AGS-3 Alters Caenorhabditis elegans Behavior after Food Deprivation via RIC-8 Activation of the Neural G Protein Gαo
Hofler C, Koelle MR. AGS-3 Alters Caenorhabditis elegans Behavior after Food Deprivation via RIC-8 Activation of the Neural G Protein Gαo. Journal Of Neuroscience 2011, 31: 11553-11562. PMID: 21832186, PMCID: PMC3161416, DOI: 10.1523/jneurosci.2072-11.2011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCaenorhabditis elegans ProteinsCells, CulturedDrosophilaFood DeprivationGTP-Binding Protein alpha Subunits, Gi-GoGuanine Nucleotide Dissociation InhibitorsGuanine Nucleotide Exchange FactorsHumansNeuronsNuclear ProteinsProtein BindingSignal TransductionConceptsAGS-3GPR proteinsG proteinsGenetic epistasis experimentsG protein GαoRegulator domainGPR domainEpistasis experimentsBiochemical fractionationChemosensory neuronsBiological functionsBiological roleFood deprivationProteinCaenorhabditisDependent fashionFood-deprived animalsActivationVivoGαoGTPDomainAnimalsNeuronsDeprivationTwo types of chloride transporters are required for GABAA receptor‐mediated inhibition in C. elegans
Bellemer A, Hirata T, Romero MF, Koelle MR. Two types of chloride transporters are required for GABAA receptor‐mediated inhibition in C. elegans. The EMBO Journal 2011, 30: 1852-1863. PMID: 21427702, PMCID: PMC3101993, DOI: 10.1038/emboj.2011.83.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedAnion Transport ProteinsBrainCaenorhabditis elegansCaenorhabditis elegans ProteinsChloridesElectrophysiologyGene Expression RegulationHydrogen-Ion ConcentrationMicroscopyMotor ActivityMutationNeuronsOocytesPlasmidsReceptors, GABA-ASymportersTransgenesXenopusConceptsCaenorhabditis elegans mutantC. elegansSynapse developmentInhibits cellBehavioral defectsCl- gradientGABAA receptor-mediated inhibitionMutantsReceptor-mediated inhibitionTransportersChloride transportersCl- channelsIdentified mutationsNeuronal expressionCl(-) cotransporterCl(-) extruderInhibitory neurotransmissionChloride gradientChloride influxElegansCellsSevere disruptionCL flowNeural activityPrincipal mechanism
2010
A Conserved Protein Interaction Interface on the Type 5 G Protein β Subunit Controls Proteolytic Stability and Activity of R7 Family Regulator of G Protein Signaling Proteins*
Porter MY, Xie K, Pozharski E, Koelle MR, Martemyanov KA. A Conserved Protein Interaction Interface on the Type 5 G Protein β Subunit Controls Proteolytic Stability and Activity of R7 Family Regulator of G Protein Signaling Proteins*. Journal Of Biological Chemistry 2010, 285: 41100-41112. PMID: 20959458, PMCID: PMC3003408, DOI: 10.1074/jbc.m110.163600.Peer-Reviewed Original ResearchConceptsR7 RGS proteinsG protein signaling (RGS) proteinsRGS proteinsDEP domainSignaling proteinsProtein interaction interfacesGenetic screenCaenorhabditis elegansRGS complexesObligate complexesProtein complexesFamily regulatorGβ5 proteinEquivalent mutationN-terminusConformational rearrangementsGβ5ProteinInteraction interfaceProteolysisMutationsRegulatorProteolytic stabilityComplexesDynamic opening
2009
RSBP-1 Is a Membrane-targeting Subunit Required by the Gαq-specific But Not the Gαo-specific R7 Regulator of G protein Signaling in Caenorhabditis elegans
Porter MY, Koelle MR. RSBP-1 Is a Membrane-targeting Subunit Required by the Gαq-specific But Not the Gαo-specific R7 Regulator of G protein Signaling in Caenorhabditis elegans. Molecular Biology Of The Cell 2009, 21: 232-243. PMID: 19923320, PMCID: PMC2808233, DOI: 10.1091/mbc.e09-07-0642.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsCell MembraneGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, Gq-G11GTP-Binding Protein RegulatorsImmunoprecipitationLocomotionMembrane ProteinsMolecular Sequence DataMusclesMutationNervous SystemOvulationProtein TransportRGS ProteinsSequence AlignmentSequence Homology, Amino AcidSignal TransductionSubcellular FractionsTransgenesConceptsR7 RGS proteinsRGS proteinsCaenorhabditis elegansEGL-10EAT-16G protein signaling (RGS) proteinsG proteinsMembrane-targeting sequenceGalpha GTPase activityC. elegans neuronsPhenocopies lossR7 regulatorMembrane associationRGS activityMembrane localizationProtein familyR7 familySignaling proteinsGTPase activityPlasma membraneGenetic studiesCultured cellsProteinR7BPElegansThe Potassium Chloride Cotransporter KCC-2 Coordinates Development of Inhibitory Neurotransmission and Synapse Structure in Caenorhabditis elegans
Tanis JE, Bellemer A, Moresco JJ, Forbush B, Koelle MR. The Potassium Chloride Cotransporter KCC-2 Coordinates Development of Inhibitory Neurotransmission and Synapse Structure in Caenorhabditis elegans. Journal Of Neuroscience 2009, 29: 9943-9954. PMID: 19675228, PMCID: PMC2737711, DOI: 10.1523/jneurosci.1989-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsChloridesFurosemideHypotonic SolutionsMotor NeuronsMusclesMutationReceptors, G-Protein-CoupledSequence HomologySexual Behavior, AnimalSodium Potassium Chloride Symporter InhibitorsSymportersSynapsesSynaptic TransmissionSynaptic VesiclesUp-RegulationConceptsEgg-laying behaviorChloride channelsC. elegans behaviorGenetic screenHSN neuronsMature neural circuitsChloride gradientFunctional analysisInhibitory neurotransmissionSynapse developmentVesicle populationsAdult mammalian brainSynaptic vesicle populationPotassium-chloride cotransporterTransport chlorideSynapse maturationPotassium-chloride cotransporter KCC2CaenorhabditisAppropriate activity levelsMammalian brainSynapse structureChloride cotransporterHypotonic conditionsLoop diuretic furosemideCoordinate development
2008
Regulation of Serotonin Biosynthesis by the G Proteins Gαo and Gαq Controls Serotonin Signaling in Caenorhabditis elegans
Tanis JE, Moresco JJ, Lindquist RA, Koelle MR. Regulation of Serotonin Biosynthesis by the G Proteins Gαo and Gαq Controls Serotonin Signaling in Caenorhabditis elegans. Genetics 2008, 178: 157-169. PMID: 18202365, PMCID: PMC2206068, DOI: 10.1534/genetics.107.079780.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCaenorhabditis elegansCaenorhabditis elegans ProteinsGene Expression Regulation, EnzymologicGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, Gq-G11Motor NeuronsMusclesOrgan SpecificityOvipositionPromoter Regions, GeneticSerotoninSignal TransductionSynapsesTryptophan HydroxylaseConceptsEgg-laying behaviorCaenorhabditis elegansG proteinsEgg-laying systemHSN motor neuronsSerotonin biosynthesisG protein GαoLevel of transcriptionEpistasis experimentsTPH-1 expressionRate-limiting enzymeGene dosageSpecific genesGalphaoGalphaqTranscriptionBiosynthesisMotor neuronsElegansTPH-1Neurotransmitter releaseGenesMultiple signalsProteinEggs
2007
A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release
Jose AM, Bany IA, Chase DL, Koelle MR. A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release. Genetics 2007, 175: 93-105. PMID: 17057248, PMCID: PMC1774992, DOI: 10.1534/genetics.106.065516.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnimals, Genetically ModifiedBiological TransportCaenorhabditis elegansCaenorhabditis elegans ProteinsEndocrine GlandsFemaleIon ChannelsMolecular Sequence DataNerve Tissue ProteinsNeurosecretory SystemsOvipositionSequence Homology, Amino AcidTRPV Cation ChannelsConceptsOCR-2Neuroendocrine cellsEgg-laying defectsTRPV channel OSM-9Heteromeric channelsG protein GDominant negative mutantTransient receptor potential channelsEndocrine cell functionOSM-9Heteromeric partnerTRPV channelsSensory neuronsSingle knockoutDetectable functionOCR-1Premature eggsSensory transductionChannel subunitsDetectable roleSubunit compositionCell functionRelease of neurotransmittersNeurotransmitter releaseSubunit combinationsC. elegans G Protein Regulator RGS-3 Controls Sensitivity to Sensory Stimuli
Ferkey DM, Hyde R, Haspel G, Dionne HM, Hess HA, Suzuki H, Schafer WR, Koelle MR, Hart AC. C. elegans G Protein Regulator RGS-3 Controls Sensitivity to Sensory Stimuli. Neuron 2007, 53: 39-52. PMID: 17196529, PMCID: PMC1855255, DOI: 10.1016/j.neuron.2006.11.015.Peer-Reviewed Original ResearchConceptsSignal transductionG protein-coupled signal transductionRGS-3G protein signaling (RGS) proteinsHeterotrimeric G proteinsSpecific RGS proteinsRGS proteinsSensory neuronsSignaling proteinsMutant animalsNegative regulatorCalcium-binding proteinsG proteinsCalcium signalingBehavioral defectsTransductionSpecific odorantsProteinDefective responseRegulatorSensory behaviorsSynaptic transmissionIntense sensory stimuliExternal stimuliSignaling
2004
RGS-7 Completes a Receptor-Independent Heterotrimeric G Protein Cycle to Asymmetrically Regulate Mitotic Spindle Positioning in C. elegans
Hess HA, Röper JC, Grill SW, Koelle MR. RGS-7 Completes a Receptor-Independent Heterotrimeric G Protein Cycle to Asymmetrically Regulate Mitotic Spindle Positioning in C. elegans. Cell 2004, 119: 209-218. PMID: 15479638, DOI: 10.1016/j.cell.2004.09.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsCell DivisionCentrosomeEmbryo, NonmammalianGTP-Binding Protein alpha SubunitsGuanine Nucleotide Exchange FactorsGuanosine TriphosphateHeterotrimeric GTP-Binding ProteinsMutationNuclear ProteinsProtein BindingRecombinant Fusion ProteinsRGS ProteinsRNA InterferenceSpindle ApparatusConceptsG protein functionRIC-8G proteinsProtein functionC. elegans embryosAsymmetric cell divisionG protein effectorsHeterotrimeric G proteinsMitotic spindle positioningG protein signalingG-protein cycleSeven-transmembrane receptorsGPR-1/2RGS domainElegans embryosGTPase activatorProtein effectorsProtein cycleMicrotubule forcesSpindle positioningProtein signalingCell cortexCell divisionGTP hydrolysisMitotic spindleActivation of EGL-47, a Gαo-Coupled Receptor, Inhibits Function of Hermaphrodite-Specific Motor Neurons to Regulate Caenorhabditis elegans Egg-Laying Behavior
Moresco JJ, Koelle MR. Activation of EGL-47, a Gαo-Coupled Receptor, Inhibits Function of Hermaphrodite-Specific Motor Neurons to Regulate Caenorhabditis elegans Egg-Laying Behavior. Journal Of Neuroscience 2004, 24: 8522-8530. PMID: 15456826, PMCID: PMC6729914, DOI: 10.1523/jneurosci.1915-04.2004.Peer-Reviewed Original ResearchConceptsHermaphrodite-specific neuronsEgg-laying behaviorTransmembrane domainEgg-laying defectsEgg-laying musclesDominant mutationsHSN motor neuronsFluorescent protein transgeneSixth transmembrane domainExtracellular N-terminusEgg-laying frequencyMotor neuronsN-terminusG proteinsTransgenic expressionGenesCaenorhabditisMild defectsReceptor isoformsInhibits functionMutationsMultiple receptorsEggsReceptorsNumber of neuronsMechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans
Chase DL, Pepper JS, Koelle MR. Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans. Nature Neuroscience 2004, 7: 1096-1103. PMID: 15378064, DOI: 10.1038/nn1316.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsDNA, ComplementaryDopamineGene TargetingGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, Gq-G11GTP-Binding ProteinsMolecular Sequence DataMotor ActivityMotor NeuronsMutationNervous SystemPhylogenyReceptors, DopamineReceptors, Dopamine D1Receptors, Dopamine D2RGS ProteinsSequence Homology, Amino AcidSequence Homology, Nucleic AcidSignal TransductionConceptsCaenorhabditis elegansDOP-3DOP-1D2-like receptorsSignaling ComplexC. elegans locomotionLocomotion defectsExtrasynaptic dopamineAntagonistic effectGαoGαqElegansD2-like dopamine receptorsD1-like receptorsSame motor neuronsPathwayReceptorsDopaminergic neuronsDopamine receptorsMotor neuronsMutantsGenesDopamineSubunitsRegulator