2024
Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula–interpeduncular nucleus pathway in mice
Tsuzuki A, Yamasaki M, Konno K, Miyazaki T, Takei N, Tomita S, Yuzaki M, Watanabe M. Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula–interpeduncular nucleus pathway in mice. Scientific Reports 2024, 14: 14193. PMID: 38902419, PMCID: PMC11189931, DOI: 10.1038/s41598-024-65076-3.Peer-Reviewed Original ResearchConceptsMHb-IPN pathwayMHb neuronsNicotine dependenceNicotinic acetylcholine receptorsAcetylcholine receptorsNicotine-related behaviorsCell surfaceImmunoelectron microscopySubunitAxonal compartmentFunctional roleNeurotransmitter releasePresynaptic terminalsSubcellular expressionPathwaySimultaneous detectionDistribution patternsSynaptic junctionsNAChRsAnatomical basisExpressionNegative controlReceptorsNeuronsAntibodies3-Hydroxykynurenine targets kainate receptors to promote defense against infection
Parada-Kusz M, Clatworthy A, Goering E, Blackwood S, Shigeta J, Mashin E, Salm E, Choi C, Combs S, Lee J, Rodriguez-Osorio C, Clish C, Tomita S, Hung D. 3-Hydroxykynurenine targets kainate receptors to promote defense against infection. Nature Chemical Biology 2024, 1-11. PMID: 38898166, DOI: 10.1038/s41589-024-01635-z.Peer-Reviewed Original ResearchKainate-sensitive glutamate receptorsHost tryptophan metabolismHost survivalBacterial infectionsPromote host survivalGlutamate receptorsLethal bacterial infectionHost-pathogenIn vivo chemical screeningTryptophan metabolismPromote defenseBacterial expansionOutcome of infectionChemical screeningZebrafish embryosAntibacterial activityKainate receptorsPathogen eradicationPathogensHostModulate immunityNervous systemInfectionMetabolismReceptors
2023
Chemogenetic regulation of the TARP-lipid interaction mimics LTP and reversibly modifies behavior
Park J, Berthoux C, Hoyos-Ramirez E, Shan L, Morimoto-Tomita M, Wang Y, Castillo P, Tomita S. Chemogenetic regulation of the TARP-lipid interaction mimics LTP and reversibly modifies behavior. Cell Reports 2023, 42: 112826. PMID: 37471228, PMCID: PMC10528344, DOI: 10.1016/j.celrep.2023.112826.Peer-Reviewed Original ResearchGlutamatergic Pathways and Receptors
Tomita S. Glutamatergic Pathways and Receptors. 2023, 197-200. DOI: 10.1007/978-3-031-15070-8_30.Peer-Reviewed Original ResearchGlutamate receptorsSynaptic transmissionSynaptic plasticityReceptor activityGlutamate receptor activityGlutamate-gated cation channelsMajor excitatory neurotransmitterGi/oG protein-coupled receptorsProtein-coupled receptorsGlutamate releaseExcitatory neurotransmitterNMDA receptorsGlutamatergic pathwaysKainate receptorsAMPA receptorsTherapeutic strategiesDistinct synapsesPostsynaptic signalingNeurological disordersSynaptic strengthGq signalingNeurodegenerative diseasesReceptorsCation channels
2022
P-088 Radiosynthesis of 6-(2-cyclobutyl-5-(methyl-11C)-3H-imidazo[4,5-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one and (2-cyclobutyl-3-(1H-indazol-5-yl)-5-[11C]methyl-3H-imidazo[4,5-b]pyridine for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein
Yu Q, Kumata K, Collier T, Tomita S, Zhang M, Liang S. P-088 Radiosynthesis of 6-(2-cyclobutyl-5-(methyl-11C)-3H-imidazo[4,5-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one and (2-cyclobutyl-3-(1H-indazol-5-yl)-5-[11C]methyl-3H-imidazo[4,5-b]pyridine for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein. Nuclear Medicine And Biology 2022, 108: s97-s98. DOI: 10.1016/s0969-8051(22)00225-6.Peer-Reviewed Original Research
2019
Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation
McCarroll MN, Gendelev L, Kinser R, Taylor J, Bruni G, Myers-Turnbull D, Helsell C, Carbajal A, Rinaldi C, Kang HJ, Gong JH, Sello JK, Tomita S, Peterson RT, Keiser MJ, Kokel D. Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation. Nature Communications 2019, 10: 4078. PMID: 31501447, PMCID: PMC6733874, DOI: 10.1038/s41467-019-11936-w.Peer-Reviewed Original ResearchConceptsParadoxical excitationGABAA receptorsCentral nervous system depressantsSerotonin 6 receptorMost anesthetic drugsDifferent neuronal targetsHuman GABAA receptorsNeuronal targetsNeuronal activityAnesthetic drugsMotor activitySerotonin receptor ligandsSedationReceptor ligandsReceptorsCaudal hindbrainAnestheticsPrimary targetPrevious studiesGABATargetNeuronsActivityBrainMolecular constituents and localization of the ionotropic GABA receptor complex in vivo
Tomita S. Molecular constituents and localization of the ionotropic GABA receptor complex in vivo. Current Opinion In Neurobiology 2019, 57: 81-86. PMID: 30784980, PMCID: PMC6629498, DOI: 10.1016/j.conb.2019.01.017.Peer-Reviewed Original ResearchConceptsNative receptor complexReceptor complexPore-forming subunitMolecular constituentsNew mechanistic insightsProtein familySubunit assemblyMajor molecular constituentsProperties of GABASynaptic localizationIonotropic GABA receptorsPrimary neuronsMechanistic insightsGABA receptor complexNative GABAReceptor regulationGABA receptorsNeuroligin-2R complexesGABAFast inhibitionPharmacological propertiesComplexesLocalizationSubunits
2018
Unexplored therapeutic opportunities in the human genome.
Oprea TI, Bologa CG, Brunak S, Campbell A, Gan GN, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J, Jadhav A, Jensen LJ, Johnson GL, Karlson A, Leach AR, Ma'ayan A, Malovannaya A, Mani S, Mathias SL, McManus MT, Meehan TF, von Mering C, Muthas D, Nguyen DT, Overington JP, Papadatos G, Qin J, Reich C, Roth BL, Schürer SC, Simeonov A, Sklar LA, Southall N, Tomita S, Tudose I, Ursu O, Vidovic D, Waller A, Westergaard D, Yang JJ, Zahoránszky-Köhalmi G. Unexplored therapeutic opportunities in the human genome. Nature Reviews. Drug Discovery 2018, 17: 377. PMID: 29567993, DOI: 10.1038/nrd.2018.52.Peer-Reviewed Original ResearchInput-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition
Chiu CQ, Martenson JS, Yamazaki M, Natsume R, Sakimura K, Tomita S, Tavalin SJ, Higley MJ. Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition. Neuron 2018, 97: 368-377.e3. PMID: 29346754, PMCID: PMC5777295, DOI: 10.1016/j.neuron.2017.12.032.Peer-Reviewed Original ResearchConceptsDendritic inhibitionInput-specific long-term potentiationNMDA-type glutamate receptorsGABAergic inhibitory synapsesSomatostatin-expressing interneuronsGABA-A receptorsNormal brain functionLong-term potentiationForms of plasticityHomeostatic cellular mechanismsGABAergic inhibitionSynaptic excitationPerisomatic inhibitionPostsynaptic spikingInhibitory synapsesLong-term plasticityGlutamate receptorsInhibitory inputsSynaptic transmissionDependent potentiationCortical circuitsGenetic deletionBrain functionNeuronal dendritesCellular mechanisms
2017
Assembly rules for GABAA receptor complexes in the brain
Martenson JS, Yamasaki T, Chaudhury NH, Albrecht D, Tomita S. Assembly rules for GABAA receptor complexes in the brain. ELife 2017, 6: e30826. PMID: 28816653, PMCID: PMC5577914, DOI: 10.7554/elife.27443.Peer-Reviewed Original ResearchGARLH Family Proteins Stabilize GABAA Receptors at Synapses
Yamasaki T, Hoyos-Ramirez E, Martenson JS, Morimoto-Tomita M, Tomita S. GARLH Family Proteins Stabilize GABAA Receptors at Synapses. Neuron 2017, 93: 1138-1152.e6. PMID: 28279354, PMCID: PMC5347473, DOI: 10.1016/j.neuron.2017.02.023.Peer-Reviewed Original ResearchConceptsInhibitory transmissionSynaptic transmissionSynaptic localizationInhibitory synaptic transmissionFast inhibitory transmissionFast synaptic transmissionIonotropic neurotransmitter receptorsLigand-gated ion channelsAuxiliary subunitsGABAA receptorsIonotropic GABANeurotransmitter receptorsNeuroligin-2GABAReceptorsAnion channelIon channelsBrainHippocampusFindingsSynapses
2016
Glutamatergic Pathways and Receptors
Tomita S. Glutamatergic Pathways and Receptors. 2016, 231-236. DOI: 10.1007/978-3-319-24551-5_29.Peer-Reviewed Original ResearchGlutamate receptorsSynaptic transmissionSynaptic plasticityReceptor activityGlutamate receptor activityGlutamate-gated cation channelsMajor excitatory neurotransmitterGi/oG protein-coupled receptorsProtein-coupled receptorsGlutamate releaseExcitatory neurotransmitterNMDA receptorsGlutamatergic pathwaysKainate receptorsAMPA receptorsTherapeutic strategiesDistinct synapsesPostsynaptic signalingNeurological disordersSynaptic strengthGq signalingNeurodegenerative diseasesReceptorsCation channelsCaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory
Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS, Picciotto MR, Castillo PE, Tomita S. CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. Neuron 2016, 92: 75-83. PMID: 27667007, PMCID: PMC5059846, DOI: 10.1016/j.neuron.2016.09.002.Peer-Reviewed Original ResearchConceptsCaMKII phosphorylation siteCaMKII substratePhosphorylation sitesDependent protein kinase IIProtein kinase IIReceptor-dependent activationNMDA receptor-dependent activationProtein phosphorylationAMPAR-mediated transmissionKinase IICaMKII-dependent enhancementLong-term potentiationCaMKII phosphorylationCellular mechanismsPhosphorylationMolecular targetsAMPA receptorsCrucial mediatorSynaptic plasticityMemory formationSynaptic insertionEssential stepSynaptic transmissionActivity-dependent strengtheningBasal transmission
2014
Synaptic localization of neurotransmitter receptors: comparing mechanisms for AMPA and GABAA receptors
Martenson JS, Tomita S. Synaptic localization of neurotransmitter receptors: comparing mechanisms for AMPA and GABAA receptors. Current Opinion In Pharmacology 2014, 20: 102-108. PMID: 25529200, PMCID: PMC4318715, DOI: 10.1016/j.coph.2014.11.011.Peer-Reviewed Original ResearchConceptsSynaptic localizationBasal transmissionGABAA receptorsSynaptic transmissionAMPA receptorsNeurotransmitter receptorsSynaptic plasticityFast synaptic transmissionMultiple receptor subunitsIonotropic neurotransmitter receptorsSynaptic insertionReceptor numberReceptor subunitsReceptorsPrecise mechanismReceptor propertiesAuxiliary subunitsTARP auxiliary subunitsRecent findingsDistinct mechanismsAMPAPostsynapsesPlasticitySynapsesPharmacology
2013
Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability
Brockie PJ, Jensen M, Mellem JE, Jensen E, Yamasaki T, Wang R, Maxfield D, Thacker C, Hoerndli F, Dunn PJ, Tomita S, Madsen DM, Maricq AV. Cornichons Control ER Export of AMPA Receptors to Regulate Synaptic Excitability. Neuron 2013, 80: 129-142. PMID: 24094107, PMCID: PMC3795439, DOI: 10.1016/j.neuron.2013.07.028.Peer-Reviewed Original ResearchConceptsGlutamatergic synaptic transmissionGlutamate-gated currentsNervous system functionIonotropic glutamate receptorsC. elegansER exportSynaptic excitabilityCargo adaptorsTransgenic wormsGenetic approachesOpposite phenotypeCornichon ProteinsGlutamate receptorsSynaptic transmissionAgonist AMPAHeterologous cellsAMPA receptorsCentral synapsesAMPAR numberSynaptic communicationReconstitution studiesHomeostatic Control of Synaptic Transmission by Distinct Glutamate Receptors
Yan D, Yamasaki M, Straub C, Watanabe M, Tomita S. Homeostatic Control of Synaptic Transmission by Distinct Glutamate Receptors. Neuron 2013, 78: 687-699. PMID: 23719165, PMCID: PMC3668311, DOI: 10.1016/j.neuron.2013.02.031.Peer-Reviewed Original ResearchConceptsKainate receptor activityGlutamate receptorsReceptor activitySynaptic transmissionNeuronal activityHigh-affinity kainate receptor subunitKainate receptor-mediated currentsDistinct glutamate receptorsReceptor-mediated currentsAMPA receptor activitySynaptic AMPA receptorsPostsynaptic glutamate receptorsKainate receptor subunitsAbundant excitatory neurotransmitterCerebellar granule cellsReceptor channel propertiesExcitatory neurotransmitterNMDA receptorsAMPA receptorsGranule cellsReceptor subunitsReceptorsSpike generationHomeostatic controlGluK5 subunits
2011
PDZ binding of TARPγ-8 controls synaptic transmission but not synaptic plasticity
Sumioka A, Brown TE, Kato AS, Bredt DS, Kauer JA, Tomita S. PDZ binding of TARPγ-8 controls synaptic transmission but not synaptic plasticity. Nature Neuroscience 2011, 14: 1410-1412. PMID: 22002768, PMCID: PMC3206644, DOI: 10.1038/nn.2952.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornBiophysicsCalcium ChannelsDisks Large Homolog 4 ProteinElectric StimulationGene Expression Regulation, DevelopmentalGuanylate KinasesHippocampusIn Vitro TechniquesLong-Term PotentiationMembrane ProteinsMiceMice, TransgenicModels, BiologicalMutationNeuronal PlasticityPatch-Clamp TechniquesPDZ DomainsSynaptic TransmissionSynaptophysinSynaptosomesDistinct functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1
Straub C, Hunt DL, Yamasaki M, Kim KS, Watanabe M, Castillo PE, Tomita S. Distinct functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1. Nature Neuroscience 2011, 14: 866-873. PMID: 21623363, PMCID: PMC3125417, DOI: 10.1038/nn.2837.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiophysical PhenomenaBiophysicsCA1 Region, HippocampalCell Line, TransformedCerebellumDisks Large Homolog 4 ProteinDizocilpine MaleateDose-Response Relationship, DrugDrug InteractionsElectric StimulationExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsGene Expression RegulationGreen Fluorescent ProteinsGuanylate KinasesHumansImmunoprecipitationIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsKainic AcidLDL-Receptor Related ProteinsLipoproteins, LDLMembrane PotentialsMembrane ProteinsMiceMice, KnockoutNeuronsPatch-Clamp TechniquesPresynaptic TerminalsProtein BindingProtein SubunitsReceptors, Kainic AcidReceptors, N-Methyl-D-AspartateSynaptophysinTransfectionTritium
2010
Hippocampal AMPA Receptor Gating Controlled by Both TARP and Cornichon Proteins
Kato AS, Gill MB, Ho MT, Yu H, Tu Y, Siuda ER, Wang H, Qian YW, Nisenbaum ES, Tomita S, Bredt DS. Hippocampal AMPA Receptor Gating Controlled by Both TARP and Cornichon Proteins. Neuron 2010, 68: 1082-1096. PMID: 21172611, PMCID: PMC3034222, DOI: 10.1016/j.neuron.2010.11.026.Peer-Reviewed Original ResearchConceptsTransmembrane AMPA receptor regulatory proteinsAMPA receptor complexesHippocampal neuronsAMPA receptorsCornichon ProteinsReceptor complexAMPA receptor traffickingReceptor regulatory proteinsGlutamate applicationKnockout miceTARP γReceptor pharmacologyCNIH-2Electrophysiological propertiesPostsynaptic densityAMPA receptor gatingSubunit combinationsProtein levelsResensitizationReceptor traffickingNeuronsPharmacologyReceptorsReceptor gatingRecombinant systemsTARP Phosphorylation Regulates Synaptic AMPA Receptors through Lipid Bilayers
Sumioka A, Yan D, Tomita S. TARP Phosphorylation Regulates Synaptic AMPA Receptors through Lipid Bilayers. Neuron 2010, 66: 755-767. PMID: 20547132, PMCID: PMC2887694, DOI: 10.1016/j.neuron.2010.04.035.Peer-Reviewed Original ResearchConceptsAMPA receptor activityTransmembrane AMPA receptor regulatory proteinsReceptor activityGlutamate receptorsSynaptic transmissionAMPA receptorsAMPA receptor-mediated synaptic transmissionPredominant excitatory neurotransmitter receptorsReceptor-mediated synaptic transmissionAMPA-type glutamate receptorsSynaptic AMPA receptorsFast synaptic transmissionIonotropic glutamate receptorsExcitatory neurotransmitter receptorsReceptor regulatory proteinsNeuronal activityNeurotransmitter receptorsPSD-95Synaptic strengthNeural circuitsReceptorsPhosphorylation-dependent mannerStargazinSynapsesTarp phosphorylation