2014
Memory Enhancement by Targeting Cdk5 Regulation of NR2B
Plattner F, Hernández A, Kistler TM, Pozo K, Zhong P, Yuen EY, Tan C, Hawasli AH, Cooke SF, Nishi A, Guo A, Wiederhold T, Yan Z, Bibb JA. Memory Enhancement by Targeting Cdk5 Regulation of NR2B. Neuron 2014, 81: 1070-1083. PMID: 24607229, PMCID: PMC4010123, DOI: 10.1016/j.neuron.2014.01.022.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCells, CulturedCyclin-Dependent Kinase 5FemaleHippocampusMaleMemoryMemory DisordersMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronal PlasticityNeuronsOrgan Culture TechniquesPhosphorylationRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsCell surface expressionReceptor cell surface expressionCyclin-dependent kinase 5Cdk5 regulationN-methyl-D-aspartate receptorsRegulatory mechanismsKinase 5NR2B functionSurface expressionNMDAR functionSubunit NR2BSynaptic plasticityEnhancerFundamental roleRegulationMemory formationNMDAR subunit NR2BCognitive enhancersValid treatment strategyPrime targetSynaptic transmissionNR2B phosphorylationNR2BPhosphorylationSurface level
2012
Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells
Jiang H, Ren Y, Yuen E, Zhong P, Ghaedi M, Hu Z, Azabdaftari G, Nakaso K, Yan Z, Feng J. Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nature Communications 2012, 3: 668. PMID: 22314364, PMCID: PMC3498452, DOI: 10.1038/ncomms1669.Peer-Reviewed Original ResearchConceptsMidbrain DA neuronsDA neuronsParkinson's diseaseDopamine utilizationDopaminergic neuronsHuman midbrain dopaminergic neuronsSpontaneous DA releaseNigral DA neuronsNigral dopaminergic neuronsDisease-modifying therapiesMidbrain dopaminergic neuronsParkin knockout miceStem cellsPluripotent stem cellsPD patientsDA releaseDA neurotransmissionDA uptakeNormal subjectsKnockout miceParkin mutationsNovel targetNeuronsOxidative stressMonoamine oxidase
2011
Impaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin*
Mandal M, Wei J, Zhong P, Cheng J, Duffney L, Liu W, Yuen E, Twelvetrees A, Li S, Li X, Kittler J, Yan Z. Impaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin*. Journal Of Biological Chemistry 2011, 286: 33719-33728. PMID: 21832090, PMCID: PMC3190808, DOI: 10.1074/jbc.m111.236521.Peer-Reviewed Original ResearchConceptsMiniature excitatory postsynaptic currentsMouse modelMutant huntingtinAMPAR-mediated synaptic transmissionHuntington Disease PathophysiologyAMPAR-mediated miniature excitatory postsynaptic currentsExcitatory postsynaptic currentsTransgenic mouse modelHD mouse modelsIsoxazolepropionic acid receptor (AMPAR) traffickingReceptor traffickingAMPA receptor traffickingPolyQ-httGlutamatergic transmissionPostsynaptic currentsSynaptic excitationSynaptic transmissionAMPA receptorsWild-type huntingtinNeuronal culturesDisease pathophysiologySynaptic functionAMPAR traffickingΑ-aminoDiminished strengthAmyloid β Peptide-(1–42) Induces Internalization and Degradation of β2 Adrenergic Receptors in Prefrontal Cortical Neurons*
Wang D, Yuen E, Zhou Y, Yan Z, Xiang Y. Amyloid β Peptide-(1–42) Induces Internalization and Degradation of β2 Adrenergic Receptors in Prefrontal Cortical Neurons*. Journal Of Biological Chemistry 2011, 286: 31852-31863. PMID: 21757762, PMCID: PMC3173113, DOI: 10.1074/jbc.m111.244335.Peer-Reviewed Original ResearchConceptsPrefrontal cortical neuronsCortical neuronsAdrenergic receptorsAMPA receptor-mediated miniature excitatory postsynaptic currentsG protein-coupled receptor kinase phosphorylationMiniature excitatory postsynaptic currentsCerebrum of miceΒAR agonist isoproterenolAmyloid precursor protein geneExcitatory postsynaptic currentsG protein-coupled receptor kinasesPrecursor protein geneProtein-coupled receptor kinasesReceptor subunit 1Mutant presenilin 1Receptor kinase phosphorylationGlutamatergic activityGlutamatergic regulationAβ bindsInduces desensitizationAβ treatmentPostsynaptic currentsΒ2-adrenergic receptorSynaptic activityAgonist isoproterenol
2010
Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons
Yuen EY, Liu W, Kafri T, Van Praag H, Yan Z. Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons. The Journal Of Physiology 2010, 588: 2361-2371. PMID: 20442266, PMCID: PMC2915513, DOI: 10.1113/jphysiol.2009.186353.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCells, CulturedCerebral CortexCofilin 1ElectrophysiologyExcitatory Postsynaptic PotentialsImmunohistochemistryLentivirusMicrofilament ProteinsNeuronal PlasticityNeuronsPhosphoric Monoester HydrolasesRatsReceptors, AMPARNA, Small InterferingRNA, ViralSynapsesSynaptic TransmissionConceptsExcitatory postsynaptic currentsCortical neuronsSynaptic transmissionSynaptic plasticityReceptor-mediated excitatory postsynaptic currentsAMPA receptor-mediated excitatory postsynaptic currentsPhosphatase SlingshotActin dynamicsAMPA receptor channelsFunction-blocking antibodiesSmall RNA interferenceAMPAR EPSCsMajor actin depolymerizing factorPostsynaptic currentsCofilin phosphatase SlingshotGluR-1Synaptic functionActin depolymerizing factorSpine morphologyAMPAR traffickingReceptor channelsActin cytoskeletonRNA interferenceNeuronsCofilin activationThe Stress Hormone Corticosterone Increases Synaptic α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors via Serum- and Glucocorticoid-inducible Kinase (SGK) Regulation of the GDI-Rab4 Complex*
Liu W, Yuen EY, Yan Z. The Stress Hormone Corticosterone Increases Synaptic α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors via Serum- and Glucocorticoid-inducible Kinase (SGK) Regulation of the GDI-Rab4 Complex*. Journal Of Biological Chemistry 2010, 285: 6101-6108. PMID: 20051515, PMCID: PMC2825404, DOI: 10.1074/jbc.m109.050229.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsCell LineCerebral CortexCorticosteroneGuanine Nucleotide Dissociation InhibitorsImmediate-Early ProteinsMiceNeuronsProtein Serine-Threonine KinasesProtein TransportRab4 GTP-Binding ProteinsRatsReceptors, AMPAReceptors, NeurotransmitterSynapsesUp-RegulationConceptsNucleotide Dissociation InhibitorSer-213Glucocorticoid-inducible kinaseRab proteinsKinase regulationDissociation inhibitorIsoxazolepropionic acid (AMPA) receptorsSmall GTPaseEarly endosomesAcid receptorsFunctional cycleCorticosteroid signalingSGK phosphorylationPlasma membraneRab4Receptor recyclingMolecular mechanismsCellular targetsCorticosteroid stress hormonesNeuronal functionPhosphorylationSurface expressionStress hormonesMembraneRegulationDelivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin
Twelvetrees A, Yuen E, Arancibia-Carcamo I, MacAskill A, Rostaing P, Lumb M, Humbert S, Triller A, Saudou F, Yan Z, Kittler J. Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin. Neuron 2010, 65: 53-65. PMID: 20152113, PMCID: PMC2841506, DOI: 10.1016/j.neuron.2009.12.007.Peer-Reviewed Original ResearchConceptsHuntingtin-associated protein 1Huntington's diseaseInhibitory postsynaptic currentsMutant huntingtinInhibitory synaptic currentsBrain excitabilityPostsynaptic currentsSynaptic inhibitionTherapeutic approachesSynaptic currentsDiseaseBrain information processingMolecular targetsSynapsesProtein 1Protein 5Protein huntingtinHuntingtinReceptorsPolyglutamine repeatsInhibitionGABAARsExcitability
2009
Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling
Joiner M, Lisé M, Yuen E, Kam A, Zhang M, Hall D, Malik Z, Qian H, Chen Y, Ulrich J, Burette A, Weinberg R, Law P, El‐Husseini A, Yan Z, Hell J. Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling. The EMBO Journal 2009, 29: 482-495. PMID: 19942860, PMCID: PMC2824466, DOI: 10.1038/emboj.2009.344.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsCalcium ChannelsCells, CulturedCerebral CortexCyclic AMP-Dependent Protein KinasesDisks Large Homolog 4 ProteinElectrophysiologyGene Expression RegulationGTP-Binding Protein alpha Subunits, GsHippocampusIntracellular Signaling Peptides and ProteinsMembrane ProteinsNeuronsRatsRats, Sprague-DawleyReceptors, Adrenergic, beta-2Receptors, AMPAConceptsUnknown molecular mechanismsMajor target proteinGluR1 surface expressionLocalized cAMPTarget proteinsMolecular mechanismsPhosphorylation of GluR1Selective regulationAdenylyl cyclaseProteinPSD-95PhosphorylationSurface expressionGlutamate receptor subunits GluR1PKAAssemblyPostsynaptic sitesCentral noradrenergic signalingHomologuesSubunit GluR1ComplexesCAMPSignalingAdrenergic receptorsStargazinUbiquitin-dependent lysosomal targeting of GABAA receptors regulates neuronal inhibition
Arancibia-Cárcamo I, Yuen E, Muir J, Lumb M, Michels G, Saliba R, Smart T, Yan Z, Kittler J, Moss S. Ubiquitin-dependent lysosomal targeting of GABAA receptors regulates neuronal inhibition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 17552-17557. PMID: 19815531, PMCID: PMC2762659, DOI: 10.1073/pnas.0905502106.Peer-Reviewed Original ResearchConceptsSynaptic inhibitionGamma2 subunitInhibitory transmissionCerebral ischemiaAnoxic insultNeuronal inhibitionGABAA receptorsExcitatory currentsSynaptic sitesLysosomal targetingPathological conditionsLysosomal activityUnknown mechanismInhibitionReceptorsMolecular mechanismsIntracellular domainTargetingPathwayIschemiaNeuropathologyEndocytic pathwayInsultAcute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory
Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 14075-14079. PMID: 19666502, PMCID: PMC2729022, DOI: 10.1073/pnas.0906791106.Peer-Reviewed Original ResearchConceptsAcute stressPrefrontal cortexGlucocorticoid receptorPotentiation of NMDARPFC pyramidal neuronsLong-term potentiationKey brain regionsCorticosteroid stress hormonesGR-dependent mechanismGlutamatergic transmissionPyramidal neuronsSynaptic transmissionBehavioral stressorsSynaptic currentsPFC neuronsBehavioral testsBrain regionsChronic stressAMPAR subunitsRecurrent excitationStress hormonesBeneficial effectsCellular mechanismsSurface expressionNMDAR
2008
Postsynaptic Density-95 (PSD-95) and Calcineurin Control the Sensitivity of N-Methyl-d-aspartate Receptors to Calpain Cleavage in Cortical Neurons
Yuen EY, Ren Y, Yan Z. Postsynaptic Density-95 (PSD-95) and Calcineurin Control the Sensitivity of N-Methyl-d-aspartate Receptors to Calpain Cleavage in Cortical Neurons. Molecular Pharmacology 2008, 74: 360-370. PMID: 18445709, PMCID: PMC2858625, DOI: 10.1124/mol.108.046813.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsCortical neuronsNR2B subunitExtrasynaptic N-methyl-D-aspartate receptorsPermeable glutamate receptorsProtein postsynaptic densityTransient forebrain ischemiaCultured cortical neuronsDependent protease calpainSynaptic NMDAR responsesPostsynaptic density-95Calpain-dependent mannerWhole-cell currentsExcitotoxic conditionsForebrain ischemiaCortical slicesNMDA treatmentNMDAR currentsNMDAR responsesNMDAR functionSubstrates of calpainGlutamate receptorsNeuronal excitabilityCalpain cleavageDensity-95Activation of 5-HT2A/C Receptors Counteracts 5-HT1A Regulation of N-Methyl-D-aspartate Receptor Channels in Pyramidal Neurons of Prefrontal Cortex*
Yuen EY, Jiang Q, Chen P, Feng J, Yan Z. Activation of 5-HT2A/C Receptors Counteracts 5-HT1A Regulation of N-Methyl-D-aspartate Receptor Channels in Pyramidal Neurons of Prefrontal Cortex*. Journal Of Biological Chemistry 2008, 283: 17194-17204. PMID: 18442977, PMCID: PMC2427346, DOI: 10.1074/jbc.m801713200.Peer-Reviewed Original ResearchConceptsPFC pyramidal neuronsExtracellular signal-regulated kinasePyramidal neuronsPrefrontal cortexNMDAR currentsN-methyl-D-aspartate receptor currentsN-methyl-D-aspartate receptor channelsSynaptic NMDAR responsesNMDAR responsesNMDAR functionActivation of ERKDendritic processesReceptor currentsPFC neuronsSignal-regulated kinaseReceptor activationMental disordersImmunocytochemical studyIntact animalsCounteractive effectsReceptor channelsInhibitory effectNeuronsCellular knockdownDependent pathway
2007
The Phosphorylation State of GluR1 Subunits Determines the Susceptibility of AMPA Receptors to Calpain Cleavage*
Yuen EY, Liu W, Yan Z. The Phosphorylation State of GluR1 Subunits Determines the Susceptibility of AMPA Receptors to Calpain Cleavage*. Journal Of Biological Chemistry 2007, 282: 16434-16440. PMID: 17428797, DOI: 10.1074/jbc.m701283200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesCalpainCells, CulturedCerebral CortexEnzyme ActivationNeuronsPhosphoprotein PhosphatasesPhosphorylationProtein Phosphatase 1Protein Processing, Post-TranslationalProtein SubunitsRatsRats, Sprague-DawleyReceptors, AMPATime FactorsConceptsCalpain cleavagePhosphorylation stateProteolytic cleavageDependent protein kinase IITerminal fusion proteinEffect of phosphorylationProtein phosphatase 1/2AProtein kinase IIPhosphorylation sitesProtein kinaseCalpain cleavage sitesGluR1 subunitKinase IIFusion proteinActive CaMKIIAMPAR currentsCalpain regulationCleavage siteIsoxazoleproprionic acid (AMPA) receptorSubunitsIonotropic glutamate receptorsN-methyl-D-aspartate receptorsPhysiological studiesExcitatory synaptic transmissionAMPA receptor currentsCalpain regulation of AMPA receptor channels in cortical pyramidal neurons
Yuen EY, Gu Z, Yan Z. Calpain regulation of AMPA receptor channels in cortical pyramidal neurons. The Journal Of Physiology 2007, 580: 241-254. PMID: 17234699, PMCID: PMC2075435, DOI: 10.1113/jphysiol.2006.122754.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalpainCells, CulturedCerebral CortexElectrophysiologyEndocytosisGerbillinaeImmunohistochemistryMaleMAP Kinase Kinase 2NeuronsNeuroprotective AgentsPatch-Clamp TechniquesPyramidal CellsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, Cell SurfaceReceptors, N-Methyl-D-AspartateStimulation, ChemicalSynapsesSynaptic TransmissionConceptsCortical pyramidal neuronsNMDA receptorsPyramidal neuronsAMPA receptorsNMDA treatmentCalpain inhibitorsIschaemia-induced depressionFast excitatory synaptic transmissionTransient ischemic insultAMPAR-mediated currentsExcitatory synaptic transmissionCalpain-dependent mannerAMPA receptor channelsSelective calpain inhibitorsExcitotoxic conditionsIschemic animalsIschemic insultNeuronal excitotoxicityAMPAR currentsAMPA responsesCortical culturesExtracellular glutamateGlutamate receptorsGlutamate triggersNeuronal excitability
2005
Activation of Dopamine D4 Receptors Induces Synaptic Translocation of Ca2+/Calmodulin-Dependent Protein Kinase II in Cultured Prefrontal Cortical Neurons
Gu Z, Jiang Q, Yuen E, Yan Z. Activation of Dopamine D4 Receptors Induces Synaptic Translocation of Ca2+/Calmodulin-Dependent Protein Kinase II in Cultured Prefrontal Cortical Neurons. Molecular Pharmacology 2005, 69: 813-822. PMID: 16365279, DOI: 10.1124/mol.105.018853.Peer-Reviewed Original ResearchConceptsD4 receptor activationDependent protein kinase IIProtein kinase IIAlpha-CaMKIID4 receptorsDopamine D4 receptorCaMKII translocationKinase IIReceptor activationF-actinSynaptic translocationPostsynaptic sitesBinding of CaMKIITrisphosphate receptor/Ca2Receptor-mediated excitatory postsynaptic currentsAMPA receptor-mediated excitatory postsynaptic currentsPhospholipase C/inositolPrefrontal cortexCalmodulin binding siteExcitatory postsynaptic currentsGlutamate receptor 1 (GluR1) subunitPrefrontal cortical neuronsD4 receptor stimulationAutophosphorylation sitesSubcellular localizationMicrotubule Regulation of N-Methyl-D-aspartate Receptor Channels in Neurons*
Yuen EY, Jiang Q, Feng J, Yan Z. Microtubule Regulation of N-Methyl-D-aspartate Receptor Channels in Neurons*. Journal Of Biological Chemistry 2005, 280: 29420-29427. PMID: 15975919, DOI: 10.1074/jbc.m504499200.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsMicrotubule depolymerizerNMDAR currentsNMDA receptorsRole of microtubulesMicrotubule regulationActin cytoskeletonBrain-derived neurotrophic factorCellular knockdownNMDAR traffickingMicrotubule-depolymerizing agentCortical pyramidal neuronsN-methyl-D-aspartate receptor channelsDendritic transportHigh NMDA concentrationsMicrotubulesPyramidal neuronsNeurotrophic factorNMDAR functionNMDA concentrationSynaptic currentsNeuronal dendritesSynaptic plasticityMicrotubule stabilizerImmunocytochemical studySerotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism
Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z. Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism. Journal Of Neuroscience 2005, 25: 5488-5501. PMID: 15944377, PMCID: PMC6724987, DOI: 10.1523/jneurosci.1187-05.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesDendritesExtracellular Signal-Regulated MAP KinasesIn Vitro TechniquesKinesinsMembrane PotentialsMicrotubulesMolecular Motor ProteinsNeuronsPatch-Clamp TechniquesPrefrontal CortexProtein SubunitsProtein TransportRatsReceptor, Serotonin, 5-HT1AReceptors, N-Methyl-D-AspartateSerotoninSerotonin 5-HT1 Receptor AgonistsSynapsesConceptsMicrotubule-dependent mechanismMEK/ERKNMDA receptorsPrefrontal cortexMicrotubule stabilityDendritic transportNMDAR interactionMicrotubule assemblyBiochemical evidenceMEK inhibitorsPFC pyramidal neuronsNMDA receptor channelsRole of serotoninCaMKIIERKNeuronal dendritesNMDAR functionMicrotubule stabilizerPathological conditionsPrimary targetReceptor channelsPyramidal neuronsNMDAR currentsSerotonin systemReceptorsRegulation of N-Methyl-D-aspartate Receptors by Calpain in Cortical Neurons*
Wu HY, Yuen EY, Lu YF, Matsushita M, Matsui H, Yan Z, Tomizawa K. Regulation of N-Methyl-D-aspartate Receptors by Calpain in Cortical Neurons*. Journal Of Biological Chemistry 2005, 280: 21588-21593. PMID: 15790561, DOI: 10.1074/jbc.m501603200.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsNMDA receptorsNMDAR currentsCortical neuronsCalpain inhibitorsCultured cortical neuronsCortical pyramidal neuronsDynamin inhibitory peptideFunction of NMDARsInhibitory peptidesInvolvement of calpainNMDAR-mediated currentsNMDAR channel functionSelective calpain inhibitorsNMDAR internalizationNMDAR overstimulationNeuroprotective mechanismsPyramidal neuronsNMDA treatmentBath applicationIntracellular injectionNR2B subunitCalcium entryPathologic functionsProlonged treatment