2025
α-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+
Blackburn J, Islam Q, Benlaouer O, Tonevitskaya S, Petitto E, Ushkaryov Y. α-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+. Toxins 2025, 17: 73. PMID: 39998090, PMCID: PMC11860464, DOI: 10.3390/toxins17020073.Peer-Reviewed Original ResearchConceptsAbsence of extracellular Ca<sup>2+</sup> anRelease of stored Ca2+Store-operated Ca<sup>2+</sup> entryExtracellular Ca<sup>2+</sup>Absence of extracellular Ca2Nerve terminalsCytosolic Ca<sup>2+</sup>Neurotransmitter releaseOpening of Ca<sup>2+</sup> channelsControl of neurotransmitter releaseRelease of neurotransmittersIntracellular storesExtracellular Ca2BAPTA-AMG protein-coupled receptorsMouse neuromuscular junctionCation ionophoreSensitive to inhibitorsCa2+Neuromuscular junctionNerveNeurotransmitterPhysiological controlReleaseInflux
2024
Absence of ATG9A and synaptophysin demixing on Rab5 mutation-induced giant endosomes
Choi J, Wu Y, Park D. Absence of ATG9A and synaptophysin demixing on Rab5 mutation-induced giant endosomes. Molecular Brain 2024, 17: 63. PMID: 39223639, PMCID: PMC11367939, DOI: 10.1186/s13041-024-01132-3.Peer-Reviewed Original ResearchConceptsGiant endosomesFormation of enlarged endosomesAutophagy-related (ATG) proteinsPool of vesiclesIntegral membrane proteinsRab5 mutantsEnlarged endosomesCore autophagy-related (ATG) proteinsEndosomal localizationIntracellular sortingMembrane proteinsEndocytic originEndosomesATG9ARab5ProteinVesiclesMutantsSegregation mechanismSynapsinCo-assemblyNerve terminalsSynaptophysinFibroblastsCellsParkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
Rafiq N, Fujise K, Rosenfeld M, Xu P, De Camilli P. Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2318943121. PMID: 38635628, PMCID: PMC11047088, DOI: 10.1073/pnas.2318943121.Peer-Reviewed Original ResearchConceptsSynaptojanin 1Endocytic factorsDA neuronsCilia-mediated signalingNerve terminalsIPSC-derived dopaminergic neuronsUbiquitin chainsUbiquitinated proteinsCiliary baseCilia lengthNeurological defectsDopaminergic neuronsProtein dynamicsDomain mutationsAssembly stateIsogenic controlsNeuronsAbnormal accumulationMutationsMiceFocal concentrationParkinsonPI(4UbiquitinEndocytosis
2023
The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volumeMutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology
Ng X, Wu Y, Lin Y, Yaqoob S, Greene L, De Camilli P, Cao M. Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology. Npj Parkinson's Disease 2023, 9: 26. PMID: 36792618, PMCID: PMC9932162, DOI: 10.1038/s41531-023-00465-5.Peer-Reviewed Original ResearchParkinson's diseaseMutant miceStriatal nerve terminalsSingle mutant miceDouble mutant miceDAergic markersDAergic terminalsAtypical parkinsonismDAergic neuronsStriatal interneuronsNeurological manifestationsAxonal pathologyDopaminergic inputNerve terminalsSynaptojanin 1Dystrophic changesPD pathogenesisKnockout miceRisk proteinsSynaptic defectsNeurodegenerative disordersParkinsonismMiceAdaptive changesDiseaseSynaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
Park D, Wu Y, Wang X, Gowrishankar S, Baublis A, De Camilli P. Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates. Nature Communications 2023, 14: 455. PMID: 36709207, PMCID: PMC9884207, DOI: 10.1038/s41467-023-36081-3.Peer-Reviewed Original ResearchConceptsMembrane proteinsSV membrane proteinsVesicle membrane proteinEctopic expression systemSynaptic vesicle proteinsSynaptic vesicle clustersSV proteinsVesicle proteinsEctopic expressionExpression systemVesicle clustersSynapsinProteinLiquid-like propertiesVesiclesDistinct classesDual roleSynapsin 1FibroblastsATG9ASynapsesExpressionDistinct phasesNerve terminalsClustersMechanotransduction events at the physiological site of touch detection
Ziolkowski L, Gracheva E, Bagriantsev S. Mechanotransduction events at the physiological site of touch detection. ELife 2023, 12: e84179. PMID: 36607222, PMCID: PMC9833821, DOI: 10.7554/elife.84179.Peer-Reviewed Original Research
2021
Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
Hutchison R, Evans K, Fox T, Yang M, Barakos J, Bedell B, Cedarbaum J, Brys M, Siderowf A, Lang A. Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial. BMC Neurology 2021, 21: 459. PMID: 34814867, PMCID: PMC8609885, DOI: 10.1186/s12883-021-02470-8.Peer-Reviewed Original ResearchConceptsDAT-SPECTParkinson's diseaseClinical trialsDisease trialsPhase 2 trialDopaminergic nerve terminalsEarly Parkinson's diseaseDisease-modifying therapiesIdiopathic Parkinson's diseaseMulticenter clinical trialParkinson's disease trialStudy design aspectsSingle photon emissionStages of progressionDegenerative parkinsonismEnrichment biomarkerResultsIn totalClinical assessmentNerve terminalsBlinded neuroradiologistsClinical diagnosisDopamine transporterMonoclonal antibodiesCentral laboratoryTrials
2019
Lower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2017
Transcellular Nanoalignment of Synaptic Function
Biederer T, Kaeser PS, Blanpied TA. Transcellular Nanoalignment of Synaptic Function. Neuron 2017, 96: 680-696. PMID: 29096080, PMCID: PMC5777221, DOI: 10.1016/j.neuron.2017.10.006.Peer-Reviewed Original ResearchQuantification of brain cholinergic denervation in Alzheimer’s disease using PET imaging with [18F]-FEOBV
Aghourian M, Legault-Denis C, Soucy J, Rosa-Neto P, Gauthier S, Kostikov A, Gravel P, Bédard M. Quantification of brain cholinergic denervation in Alzheimer’s disease using PET imaging with [18F]-FEOBV. Molecular Psychiatry 2017, 22: 1531-1538. PMID: 28894304, DOI: 10.1038/mp.2017.183.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBrainCase-Control StudiesCholinergic AgentsCholinergic NeuronsFemaleFluorodeoxyglucose F18HumansMaleMiddle AgedPiperidinesPositron-Emission TomographyPresynaptic TerminalsRadioactive TracersVesicular Acetylcholine Transport ProteinsConceptsMini-Mental State ExaminationStandardized uptake value ratioAlzheimer's diseaseCortical areasPresynaptic cholinergic nerve terminalsAmyloid-beta tracerNumerous cortical areasCognitive scalesCholinergic nerve terminalsUptake value ratioVesicular acetylcholine transporterMultiple cortical areasNew PET radiotracersVoxel-wise t-testsCholinergic denervationCholinergic terminalsCholinergic degenerationControl subjectsAD patientsCholinergic lossNerve terminalsAD groupHealthy subjectsAcetylcholine transporterAD subjects
2015
Neurotransmitters and Neurohormones
Levitan I, Kaczmarek L. Neurotransmitters and Neurohormones. 2015, 213-238. DOI: 10.1093/med/9780199773893.003.0010.ChaptersNervous systemNearby glial cellsRole of neurotransmittersSpecific transporter proteinsExtracellular spaceGlial cellsNerve terminalsPresynaptic terminalsTransporter proteinsIntercellular communicationTarget cellsGreat diversityNeuropeptidesNeurotransmittersMultitude of chemicalsCellsAcetylcholineReuptakeCatecholaminesGABANeuronsNeurohormones
2014
Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel 18F-Labeled Tracer for Imaging Myocardial Innervation
Sinusas AJ, Lazewatsky J, Brunetti J, Heller G, Srivastava A, Liu YH, Sparks R, Puretskiy A, Lin SF, Crane P, Carson RE, Lee LV. Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel 18F-Labeled Tracer for Imaging Myocardial Innervation. Journal Of Nuclear Medicine 2014, 55: 1445-1451. PMID: 24994931, DOI: 10.2967/jnumed.114.140137.Peer-Reviewed Original ResearchConceptsAdministered activityBlood-pool standardized uptake valuesPhase 1 clinical trialCardiac nerve terminalsCardiac imagingMSv/MBqMean effective doseStandardized uptake valueRadiation doseOLINDA/EXMPatient radiation doseRadiation dose estimatesAdverse eventsBlood pressureWhole-body imagesClinical trialsBlood radioactivityMyocardial innervationNerve terminalsUrinary bladderHealthy subjectsLiver ratioHeart rateLung activityMyocardial uptake
2011
The Expression Level of Ecto-NTP Diphosphohydrolase1/CD39 Modulates Exocytotic and Ischemic Release of Neurotransmitters in a Cellular Model of Sympathetic Neurons
Corti F, Olson K, Marcus A, Levi R. The Expression Level of Ecto-NTP Diphosphohydrolase1/CD39 Modulates Exocytotic and Ischemic Release of Neurotransmitters in a Cellular Model of Sympathetic Neurons. Journal Of Pharmacology And Experimental Therapeutics 2011, 337: 524-532. PMID: 21325440, PMCID: PMC3083107, DOI: 10.1124/jpet.111.179994.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAntigens, CDApyraseBlotting, WesternDNA PrimersDopamineExocytosisGene Expression Regulation, EnzymologicGene SilencingIschemiaNerve Growth FactorsNeuronsNeurotransmitter AgentsNorepinephrinePC12 CellsPotassiumRatsReceptors, Purinergic P2XReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSympathetic Nervous SystemConceptsE-NTPDase1/CD39CD39 expressionTransmitter ATPSympathetic neuronsDopamine releaseExcessive catecholamine releaseNerve growth factor-differentiated PC12 cellsSympathetic nerve terminalsPC12 cellsExocytosis of ATPCellular modelRelease of ATPCD39 overexpressionIschemic releasePrejunctional siteSympathetic nervesCardiac dysfunctionMyocardial ischemiaCatecholamine releaseCD39 deletionNerve terminalsDepolarization-induced exocytosisAutocrine mannerDiphosphohydrolase-1Predominant catecholamine
2009
Wide-Field and Two-Photon Imaging of Brain Activity with Voltage and Calcium-Sensitive Dyes
Homma R, Baker BJ, Jin L, Garaschuk O, Konnerth A, Cohen LB, Bleau CX, Canepari M, Djurisic M, Zecevic D. Wide-Field and Two-Photon Imaging of Brain Activity with Voltage and Calcium-Sensitive Dyes. Methods In Molecular Biology 2009, 489: 43-79. PMID: 18839087, DOI: 10.1007/978-1-59745-543-5_3.Peer-Reviewed Original ResearchConceptsCalcium-sensitive dyeOlfactory bulb glomeruliCell typesBrain activityIndividual cell typesOlfactory receptor neuronsNerve terminalsSynaptic activityVoltage-sensitive dyeSpike activityTwo-photon imagingVivo preparationMammalian brainReceptor neuronsIndividual neuronsIon-sensitive dyesNeuronsTwo-photon microscopyBrainMembrane potentialLow sensitivitySensitive dyeNoseOutput spike trainsSpike trains
2008
Lrp4 Is a Receptor for Agrin and Forms a Complex with MuSK
Kim N, Stiegler A, Cameron T, Hallock P, Gomez A, Huang J, Hubbard S, Dustin M, Burden S. Lrp4 Is a Receptor for Agrin and Forms a Complex with MuSK. Cell 2008, 135: 334-342. PMID: 18848351, PMCID: PMC2933840, DOI: 10.1016/j.cell.2008.10.002.Peer-Reviewed Original ResearchConceptsCongenital myasthenic syndromeSynaptic differentiationSpecialized release sitesAgrin activates MuSKNeuromuscular synapse formationReceptor tyrosine kinasesGroup of neuromuscular disordersLDLR familyMuSK activationDownstream effectorsSkeletal muscle fibersMuSK phosphorylationPostsynaptic proteinsPresynaptic nerve terminalsTyrosine kinaseMyasthenic syndromeSynapse formationMuscle membraneNerve terminalsAgrinMotor neuronsNeuromuscular synapsesRelease sitesActive zoneReceptors
2005
α-Synuclein Cooperates with CSPα in Preventing Neurodegeneration
Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC. α-Synuclein Cooperates with CSPα in Preventing Neurodegeneration. Cell 2005, 123: 383-396. PMID: 16269331, DOI: 10.1016/j.cell.2005.09.028.Peer-Reviewed Original ResearchConceptsAbundant synaptic vesicle proteinsEndogenous synucleinNeuronal survivalNerve terminalsParkinson's diseaseProgressive neurodegenerationSynaptic vesicle proteinsAlpha-synucleinDownstream mechanismsNeurodegenerationVivo activitySNARE complex assemblyCSPalphaTransgenic expressionDiseaseMicePhysiological roleCochaperone functionVesicle proteinsSNARE proteinsComplex assemblyInjuryDeletionSynucleinImaging Brain Activity With Voltage- and Calcium-Sensitive Dyes
Baker BJ, Kosmidis EK, Vucinic D, Falk CX, Cohen LB, Djurisic M, Zecevic D. Imaging Brain Activity With Voltage- and Calcium-Sensitive Dyes. Cellular And Molecular Neurobiology 2005, 25: 245-282. PMID: 16050036, PMCID: PMC11529562, DOI: 10.1007/s10571-005-3059-6.Peer-Reviewed Original ResearchConceptsVoltage-sensitive dyeCalcium-sensitive dyeLight sourceDark noiseVibrational noiseOptical recordingRandom emissionBrain activityFluorescent protein sensorOlfactory receptor neuronsNerve terminalsOlfactory bulbSpike activityNoise ratioCell bodiesReceptor neuronsPhotonsOpticsOptimal signalNeuronsIndividual cell typesKinds of noiseExternal sourcesVoltageCell types
2004
ATP-Induced Modulation of Norepinephrine Exocytosis in Human and Porcine Heart: Role of E-NTPDase1/CD39.
Machida T, Heerdt P, Reid A, Schaefer U, Silver R, Broekman M, Marcus A, Levi R. ATP-Induced Modulation of Norepinephrine Exocytosis in Human and Porcine Heart: Role of E-NTPDase1/CD39. Blood 2004, 104: 1869. DOI: 10.1182/blood.v104.11.1869.1869.Peer-Reviewed Original ResearchE-NTPDase1/CD39NE exocytosisSympathetic nerve terminalsNE releaseNovel therapeutic approachesMyocardial ischemiaNerve terminalsTherapeutic approachesCardiac sympathetic nerve terminalsCoronary vascular dysfunctionSympathetic nerve endingsIschemic heart diseaseActivation of ATPGuinea pig heartsImportant modulatory roleAnti-thrombotic agentsCause of dysfunctionDepolarization of synaptosomesRelease of ATPAdrenergic neurotransmissionCardiac neuronsIschemic complicationsSympathetic terminalsP2X purinoceptorsVascular dysfunctionImpaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking
Paolo G, Moskowitz HS, Gipson K, Wenk MR, Voronov S, Obayashi M, Flavell R, Fitzsimonds RM, Ryan TA, Camilli P. Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking. Nature 2004, 431: 415-422. PMID: 15386003, DOI: 10.1038/nature02896.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBiological TransportCells, CulturedClathrinElectric ConductivityEndocytosisExocytosisGene DeletionKineticsMiceMice, KnockoutNeuronsPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)Presynaptic TerminalsSynaptic TransmissionSynaptic VesiclesConceptsClathrin coat dynamicsSynaptic vesicle cycleSynaptic vesicle exocytosisSynaptic vesicle traffickingSecond messenger moleculesEarly postnatal lethalityEndocytic intermediatesVesicle traffickingMembrane proteinsVesicle cycleVesicle exocytosisPostnatal lethalityCell regulationRecycling kineticsMessenger moleculesBiochemical studiesSynaptic defectsDirect interactionImportant functionsCritical roleMultiple stepsReleasable poolRegulationNerve terminalsDephosphorylation
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