2024
Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation
Lallai V, Lam T, Garcia-Milian R, Chen Y, Fowler J, Manca L, Piomelli D, Williams K, Nairn A, Fowler C. Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation. Biomolecules 2024, 14: 1143. PMID: 39334909, PMCID: PMC11430348, DOI: 10.3390/biom14091143.Peer-Reviewed Original ResearchConceptsImmediate early gene c-fosChronic THC exposureEarly gene c-fosCannabinoid 1 receptorGene c-fosSex-specific mannerTHC exposurePsychoactive componentExtracellular vesiclesCentral signaling mechanismDrug effectsTHCChoroid plexus epithelial cellsFemale ratsC-fosPlexus epithelial cellsBrainCannabisRelease of EVsRegulate intercellular communicationCerebrospinal fluidEpithelial cellsIntercellular signaling mediatorsEV signalingIntercellular communication
2023
Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome
Ketchesin K, Becker-Krail D, Xue X, Wilson R, Lam T, Williams K, Nairn A, Tseng G, Logan R. Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome. Journal Of Proteome Research 2023, 22: 2377-2390. PMID: 37311105, PMCID: PMC10392613, DOI: 10.1021/acs.jproteome.3c00126.Peer-Reviewed Original ResearchConceptsNucleus accumbensDiurnal regulationMouse nucleus accumbensPhase-dependent regulationBrain regionsDiurnal rhythmAdministration of psychostimulantsEffects of cocaineSubstance use disordersDifferential effectsMolecular rhythmsProtein rhythmsQuantitative proteomicsProteomic dataProteomeMorphine administrationUse of substancesRhythm alterationsGlucocorticoid signalingUse disordersMorphineSubstance useProtein expressionCocaineSignificant alterations
2022
DARPP-32/protein phosphatase 1 regulates Rasgrp2 as a novel component of dopamine D1 receptor signaling in striatum
Kuroiwa M, Shuto T, Nagai T, Amano M, Kaibuchi K, Nairn A, Nishi A. DARPP-32/protein phosphatase 1 regulates Rasgrp2 as a novel component of dopamine D1 receptor signaling in striatum. Neurochemistry International 2022, 162: 105438. PMID: 36351540, DOI: 10.1016/j.neuint.2022.105438.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Phosphatase 1DARPP-32Receptor-induced phosphorylationPKA-dependent phosphorylationPKA/DARPPPP1 inhibitorPP1 substratesPP1 inhibitionPKA sitesRap1 activationOkadaic acidRASGRP2Novel componentRap1GAPPhosphorylationDARPP-32 knockout micePhospho-Thr34 DARPP-32Receptor activationPKAKnockout miceReceptor stimulationPP2A.Ser499Rap1Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits
Lee E, Liu Z, Nguyen N, Nairn A, Chang AN. Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits. Journal Of Biological Chemistry 2022, 298: 102296. PMID: 35872014, PMCID: PMC9418503, DOI: 10.1016/j.jbc.2022.102296.Peer-Reviewed Original ResearchConceptsMyosin light chain phosphataseRegulatory light chainRegulatory subunitCatalytic subunitPhosphatase catalytic subunitMain catalytic subunitSmooth muscle myosin light chain phosphataseNon-muscle cellsMuscle myosin light chain phosphataseMyosin regulatory light chainMyosin light chain kinaseLight chain kinasePP1cβTrimeric proteinConditional knockout miceLight chain phosphatasePhosphatase activitySubunitsPhosphate/Chain kinaseMuscle pathogenesisPhysiological regulationKnockout animalsMain isoformsProtein
2018
Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology
Rapanelli M, Frick L, Jindachomthong K, Xu J, Ohtsu H, Nairn A, Pittenger C. Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology. Neuroscience 2018, 392: 172-179. PMID: 30278251, PMCID: PMC6204318, DOI: 10.1016/j.neuroscience.2018.09.035.Peer-Reviewed Original ResearchConceptsHDC-KO miceMitogen-activated protein kinaseHistamine receptorsWT animalsDorsal striatumH3R activationTic-like movementsStriatonigral medium spiny neuronsAkt phosphorylationMedium spiny neuronsWild-type miceRare genetic causeHistamine dysregulationAgonist treatmentKO miceSpiny neuronsTic disordersTic pathophysiologyStriatal signalingMouse modelNeuropsychiatric diseasesKO modelRepetitive movementsStriatumMiceStriatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons
Li D, Musante V, Zhou W, Picciotto MR, Nairn AC. Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons. Journal Of Biological Chemistry 2018, 293: 11179-11194. PMID: 29802198, PMCID: PMC6052221, DOI: 10.1074/jbc.ra117.001519.Peer-Reviewed Original ResearchConceptsSerine/threonine phosphatase PP2AStriatin-interacting phosphataseRNA knockdown approachB subunitSTRIPAK complexPhosphatase PP2AProtein phosphataseMultiprotein complexesKnockdown approachStriatin familyMutant constructsStriatal neuronal culturesPP2ANeuronal developmentPrimary striatal neuronal culturesDendritic phenotypeKnockdown modelSynapse formationSubunitsSpine developmentSelective roleReduced expressionNeuron maturationNeuronal culturesStriatal neuronsMaking brain proteomics true to type
Wilson RS, Nairn AC. Making brain proteomics true to type. Nature Biotechnology 2018, 36: 149-150. PMID: 29406511, DOI: 10.1038/nbt.4077.Peer-Reviewed Original Research
2017
A multiregional proteomic survey of the postnatal human brain
Carlyle BC, Kitchen RR, Kanyo JE, Voss EZ, Pletikos M, Sousa AMM, Lam TT, Gerstein MB, Sestan N, Nairn AC. A multiregional proteomic survey of the postnatal human brain. Nature Neuroscience 2017, 20: 1787-1795. PMID: 29184206, PMCID: PMC5894337, DOI: 10.1038/s41593-017-0011-2.Peer-Reviewed Original ResearchConceptsProteomic surveyResident plasma membrane proteinsPostnatal human brainProtein dataPlasma membrane proteinsProtein abundance differencesQuantitative tandem mass spectrometryPost-translational eventsWhole transcriptome sequencingRNA expression dataMembrane proteinsFunctional variationExpression dataAbundance differencesBrain regionsTandem mass spectrometryHuman brainSimilar cortical regionsMass spectrometryEarly infancyRNACortical regionsSequencingProteinAbundanceARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase)
Andrade EC, Musante V, Horiuchi A, Matsuzaki H, Brody AH, Wu T, Greengard P, Taylor JR, Nairn AC. ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase). Journal Of Neuroscience 2017, 37: 2709-2722. PMID: 28167675, PMCID: PMC5354324, DOI: 10.1523/jneurosci.4559-15.2017.Peer-Reviewed Original ResearchConceptsSerine/threonine protein phosphataseSerine/threonine kinase 3Threonine protein phosphataseARPP-16Protein phosphataseKinase 3Protein phosphatase 2AProtein kinase A (PKA) signalingSmall acid-soluble proteinsKinase A SignalingAcid-soluble proteinsActivation of PKAPP2A substratesPhosphatase 2AARPP-16/19Heterotrimeric formMarked dephosphorylationSignal transductionSelective inhibitorPP2AA SignalingUnknown functionStriatal medium spiny neuronsMedium spiny neuronsSer46
2016
Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution
Nishi A, Matamales M, Musante V, Valjent E, Kuroiwa M, Kitahara Y, Rebholz H, Greengard P, Girault JA, Nairn AC. Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution. Journal Of Biological Chemistry 2016, 292: 1462-1476. PMID: 27998980, PMCID: PMC5270488, DOI: 10.1074/jbc.m116.752402.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Ser-97PKA signalingDARPP-32Thr-34Activation of PP2A.Multiple cellular levelsProtein DARPP-32Phosphatase 1Heterotrimer complexPKA actionPhosphorylation stateNuclear localizationThr-75Phosphatase assaysDephosphorylationDARPP-32 phosphorylationCultured striatal neuronsSer-130Cellular levelSignalingPhosphorylationMajor siteStriatal neuronsGlutamate
2015
STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease
Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC. STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1202-1207. PMID: 25583483, PMCID: PMC4313846, DOI: 10.1073/pnas.1417423112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCorpus StriatumCyclic AMP Response Element-Binding ProteinDown-RegulationGene Expression Regulation, EnzymologicHEK293 CellsHumansMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 3MPTP PoisoningProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyUbiquitin-Protein LigasesUbiquitinationUp-RegulationConceptsE3 ubiquitin ligase ParkinSubstantia nigra pars compactaPathophysiology of PDProtein tyrosine phosphataseUbiquitin ligase ParkinSporadic Parkinson's diseaseE3 ligase ParkinRegulation of ParkinParkinson's diseaseTyrosine phosphataseParkin mutantsE3 ligaseProteasome systemDopaminergic neuronsDownstream targetsAutosomal recessive juvenile parkinsonismNovel substrateSTEP61ParkinCellular modelSTEP61 levelsSNc dopaminergic neuronsProtein levelsFunction contributesERK1/2
2014
Decoding neuroproteomics: integrating the genome, translatome and functional anatomy
Kitchen RR, Rozowsky JS, Gerstein MB, Nairn AC. Decoding neuroproteomics: integrating the genome, translatome and functional anatomy. Nature Neuroscience 2014, 17: 1491-1499. PMID: 25349915, PMCID: PMC4737617, DOI: 10.1038/nn.3829.Peer-Reviewed Original Research
2013
Recent advances in quantitative neuroproteomics
Craft GE, Chen A, Nairn AC. Recent advances in quantitative neuroproteomics. Methods 2013, 61: 186-218. PMID: 23623823, PMCID: PMC3891841, DOI: 10.1016/j.ymeth.2013.04.008.Peer-Reviewed Original Research
2006
2‐Deoxyglucose and NMDA inhibit protein synthesis in neurons and regulate phosphorylation of elongation factor‐2 by distinct mechanisms
Maus M, Torrens Y, Gauchy C, Bretin S, Nairn A, Glowinski J, Premont J. 2‐Deoxyglucose and NMDA inhibit protein synthesis in neurons and regulate phosphorylation of elongation factor‐2 by distinct mechanisms. Journal Of Neurochemistry 2006, 96: 815-824. PMID: 16405506, DOI: 10.1111/j.1471-4159.2005.03601.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolitesBlotting, WesternCalciumCarbonyl Cyanide m-Chlorophenyl HydrazoneCells, CulturedCerebral CortexDeoxyglucoseDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnzyme InhibitorsExcitatory Amino Acid AgonistsIonophoresLeucineMiceModels, BiologicalN-MethylaspartateNeuronsOligomycinsPeptide Elongation Factor 2PhosphorylationProtein KinasesProtein Synthesis InhibitorsPyruvic AcidSodium AzideTime FactorsTOR Serine-Threonine KinasesTritiumConceptsCortical neuronsExcitatory amino acid releaseImine hydrogen maleateNMDA receptor antagonistAMP kinaseAmino acid releaseNeuronal protein synthesisCytosolic free Ca2Protein synthesisCerebral ischaemiaReceptor antagonistBrain damageNeuronal metabolismMetabolic impairmentNMDADistinct mechanismsCytosolic Ca2NeuronsMetabolic deprivationAcid releaseSecondary releaseProtein synthesis inhibitionSynthesis inhibitionElongation factor eEF-2ATP levels
2005
A molecular switch for translational control in taste memory consolidation
Belelovsky K, Elkobi A, Kaphzan H, Nairn A, Rosenblum K. A molecular switch for translational control in taste memory consolidation. European Journal Of Neuroscience 2005, 22: 2560-2568. PMID: 16307598, DOI: 10.1111/j.1460-9568.2005.04428.x.Peer-Reviewed Original ResearchConceptsEukaryotic elongation factor 2Protein synthesisEEF2 phosphorylationKinase 2 activationElongation factor 2Translational regulationTranslation initiationTranslational controlS6K1 phosphorylationMolecular switchSwitch-like effectNeuronal proteinsPhosphorylationElongation rateRate-limiting stepFactor 2Taste memory consolidationSynaptoneurosomal fractionsExpressionTemporal patternsInitiation rateProtein
2003
Adenylyl cyclase-dependent form of chemical long-term potentiation triggers translational regulation at the elongation step
Chotiner J, Khorasani H, Nairn A, O’Dell T, Watson J. Adenylyl cyclase-dependent form of chemical long-term potentiation triggers translational regulation at the elongation step. Neuroscience 2003, 116: 743-752. PMID: 12573716, DOI: 10.1016/s0306-4522(02)00797-2.Peer-Reviewed Original ResearchConceptsEukaryotic elongation factor 2Elongation factor 2Elongation stepProtein synthesisTotal protein synthesisChemical long-term potentiationMessenger RNALong-term potentiationN-methyl-D-aspartate (NMDA) receptor-dependent formInhibition of translationFactor 2Long-term potentiation inductionTranslational regulationProtein ArcAdenylyl cyclase signalingAdenylyl cyclase activationSynaptic activityCyclase signalingN-methyl-D-aspartate (NMDA) receptor activationPersistent maintenanceReceptor-dependent formHippocampal long-term potentiationPhosphorylationRegulationRNA
2002
N-Methyl-D-aspartate receptor activation inhibits protein synthesis in cortical neurons independently of its ionic permeability properties
Gauchy C, Nairn A, Glowinski J, Prémont J. N-Methyl-D-aspartate receptor activation inhibits protein synthesis in cortical neurons independently of its ionic permeability properties. Neuroscience 2002, 114: 859-867. PMID: 12379242, DOI: 10.1016/s0306-4522(02)00322-6.Peer-Reviewed Original ResearchConceptsCortical neuronsAbsence of externalNMDA treatmentTransient cerebral ischemiaAspartate receptor activationGlutamate-induced increaseThapsigargin-sensitive poolMobilization of intracellularProtein synthesisCerebral ischemiaNMDA receptorsNMDAReceptor activationTransient risePresence of externalNeuronsCGP-37157D-serineFree mediumIntracellularIonic permeability propertiesTreatmentSustained releaseIschemiaBlockade
2001
Opposing Changes in Phosphorylation of Specific Sites in Synapsin I During Ca2+-Dependent Glutamate Release in Isolated Nerve Terminals
Jovanovic J, Sihra T, Nairn A, Hemmings H, Greengard P, Czernik A. Opposing Changes in Phosphorylation of Specific Sites in Synapsin I During Ca2+-Dependent Glutamate Release in Isolated Nerve Terminals. Journal Of Neuroscience 2001, 21: 7944-7953. PMID: 11588168, PMCID: PMC6763853, DOI: 10.1523/jneurosci.21-20-07944.2001.Peer-Reviewed Original ResearchConceptsDependent dephosphorylationProtein phosphatase 2AMultiple protein kinasesPhosphorylation site 1Protein phosphatase 2BSynapsin IPhosphatase 2APhosphorylation sitesPhosphatase 2BSynapsin functionProtein kinaseDependent phosphorylationSynapsin I phosphorylationDephosphorylation processNeuronal phosphoproteinSynapsin I.Synaptic vesiclesCalcineurin activityPhosphorylationI phosphorylationDephosphorylationNeurotransmitter releaseSpecific sitesExcellent substrateSite 1A Novel Cyclin Provides a Link between Dopamine and RNA Processing
Nairn A, Greengard P. A Novel Cyclin Provides a Link between Dopamine and RNA Processing. Neuron 2001, 32: 174-176. PMID: 11683987, DOI: 10.1016/s0896-6273(01)00469-x.Peer-Reviewed Original ResearchRegulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic glutamate receptors
Liu F, Ma X, Ule J, Bibb J, Nishi A, DeMaggio A, Yan Z, Nairn A, Greengard P. Regulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic glutamate receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 11062-11068. PMID: 11572969, PMCID: PMC58683, DOI: 10.1073/pnas.191353898.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium ChannelsCasein KinasesCyclin-Dependent Kinase 5Cyclin-Dependent KinasesDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsIn Vitro TechniquesKineticsMaleMembrane PotentialsMethoxyhydroxyphenylglycolMiceMice, Inbred C57BLNeostriatumNerve Tissue ProteinsNeuronsPatch-Clamp TechniquesPhosphoproteinsPhosphorylationPhosphoserinePhosphothreonineProtein KinasesReceptors, Metabotropic GlutamateConceptsCasein kinase 1Cyclin-dependent kinase 5Ser-137Thr-75CK1 activityKinase 1Kinase 5DARPP-32Regulation of Cdk5Neuronal protein kinaseActivation of Cdk5Cellular functionsProtein kinaseDNA repairEnhanced phosphorylationFirst messengersCdk5 activitySpecific inhibitorCdk5Effects of DHPGMetabotropic glutamate receptorsNeurite outgrowthIC261Glutamate receptorsDHPG-induced increase