2023
Multiple Subthreshold GPCR Signals Combined by the G-Proteins Gαq and Gαs Activate the Caenorhabditis elegans Egg-Laying Muscles
Olson A, Butt A, Christie N, Shelar A, Koelle M. Multiple Subthreshold GPCR Signals Combined by the G-Proteins Gαq and Gαs Activate the Caenorhabditis elegans Egg-Laying Muscles. Journal Of Neuroscience 2023, 43: 3789-3806. PMID: 37055179, PMCID: PMC10219013, DOI: 10.1523/jneurosci.2301-22.2023.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsMultiple G protein-coupled receptorsMuscle cellsMuscle activitySerotonin G protein-coupled receptorsDesigner G protein-coupled receptorsIntact animalsG proteinsEndogenous G protein-coupled receptorsIndividual G protein-coupled receptorsGPCR signalsCalcium activityEgg-laying musclesSerotoninIndividual neuronsDouble knockoutNeuronsBehavioral outcomesMuscleMost cellsG protein GαqCellsSubthreshold signalEgg-laying systemSER-1
2022
Using NeuroPAL Multicolor Fluorescence Labeling to Identify Neurons in C. elegans
Santiago E, Shelar A, Christie N, Lewis‐Hayre M, Koelle M. Using NeuroPAL Multicolor Fluorescence Labeling to Identify Neurons in C. elegans. Current Protocols 2022, 2: e610. PMID: 36521003, PMCID: PMC10257892, DOI: 10.1002/cpz1.610.Peer-Reviewed Original Research
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
2019
Serotonin and neuropeptides are both released by the HSN command neuron to initiate C. elegans egg laying
Brewer JC, Olson AC, Collins KM, Koelle MR. Serotonin and neuropeptides are both released by the HSN command neuron to initiate C. elegans egg laying. PLOS Genetics 2019, 15: e1007896. PMID: 30677018, PMCID: PMC6363226, DOI: 10.1371/journal.pgen.1007896.Peer-Reviewed Original ResearchConceptsHermaphrodite-specific neuronsEgg-laying defectsNLP-3C. elegansEgg-laying musclesEgg-laying circuitDirect postsynaptic targetsEgg-laying behaviorSerotonergic Hermaphrodite Specific NeuronsMuscle cellsSmall molecule neurotransmittersNull mutantsHSN neuronsDouble mutantSingle mutantsMutant animalsSerotonergic neuronsWild-type animalsSevere defectsMutantsElegansNeuropeptide substance PMammalian brainEggsSpecific neurons
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
Neural Architecture of Hunger-Dependent Multisensory Decision Making in C. elegans
Ghosh DD, Sanders T, Hong S, McCurdy LY, Chase DL, Cohen N, Koelle MR, Nitabach MN. Neural Architecture of Hunger-Dependent Multisensory Decision Making in C. elegans. Neuron 2016, 92: 1049-1062. PMID: 27866800, PMCID: PMC5147516, DOI: 10.1016/j.neuron.2016.10.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutocrine CommunicationCaenorhabditis elegansDecision MakingFeedbackHungerInterneuronsModels, NeurologicalNerve NetNeuronsNeuropeptidesRewardActivity 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
Postsynaptic ERG Potassium Channels Limit Muscle Excitability to Allow Distinct Egg-Laying Behavior States in Caenorhabditis elegans
Collins KM, Koelle MR. Postsynaptic ERG Potassium Channels Limit Muscle Excitability to Allow Distinct Egg-Laying Behavior States in Caenorhabditis elegans. Journal Of Neuroscience 2013, 33: 761-775. PMID: 23303953, PMCID: PMC3542984, DOI: 10.1523/jneurosci.3896-12.2013.Peer-Reviewed Original ResearchConceptsEgg-laying musclesBody bendsUNC-103Caenorhabditis elegansCalcium transientsTwo-state behaviorERG potassium channelsMutantsERG channelsPotassium channelsInactive phaseEggsDistinct behavioral statesMuscle excitabilityPostsynaptic excitabilityPostsynaptic sitesERG functionCaenorhabditisCalcium imagingElegansFurther adjustmentExcitabilityRhythmic excitationMuscleBehavioral statesLIN-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 cellsProteinR7BPElegansChapter 2 Insights into RGS Protein Function from Studies in Caenorhabditis elegans
Porter MY, Koelle MR. Chapter 2 Insights into RGS Protein Function from Studies in Caenorhabditis elegans. Progress In Nucleic Acid Research And Molecular Biology 2009, 86: 15-47. PMID: 20374712, DOI: 10.1016/s1877-1173(09)86002-x.Peer-Reviewed Original ResearchConceptsRGS proteinsGα proteinsMultiple RGS proteinsRGS protein functionG protein αRGS domainCaenorhabditis elegansProtein subfamiliesC. elegansGα genesProtein functionChapter 2 InsightsVivo functionNematode wormsPhysiological functionsProtein αProteinElegansSubfamiliesSuch specificityDifferent cellsRGSOrthologsCaenorhabditisMammalsThe 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