2025
Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse
Hanke-Gogokhia C, Zapadka T, Finkelstein S, Arshavsky V, Demb J. Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse. Advances In Experimental Medicine And Biology 2025, 1468: 325-330. PMID: 39930217, DOI: 10.1007/978-3-031-76550-6_54.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndocytosisExocytosisHumansMiceRetinal Rod Photoreceptor CellsSynapsesSynaptic TransmissionSynaptic VesiclesConceptsSynaptic vesicle exocytosisSynaptic vesicle recyclingPhotoreceptor ribbon synapseVesicle exocytosisVesicle recyclingVesicle cycleVesicle releaseRibbon synapseProtein synthesisProperties of synaptic transmissionMolecular componentsMouse rodsSynaptic terminalsRod cellsProteinVesiclesRod photoreceptorsDim lightSynaptic transmissionInner segmentsCellsExocytosisEndocytosisOuter segmentsEnergy production
2024
Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release
Bose D, Bera M, Norman C, Timofeeva Y, Volynski K, Krishnakumar S. Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release. Nature Communications 2024, 15: 10741. PMID: 39738049, PMCID: PMC11685451, DOI: 10.1038/s41467-024-54960-1.Peer-Reviewed Original ResearchConceptsSynaptotagmin-7Synaptotagmin-1Protein machinerySNARE complex assemblyFusion clampExocytosis processVesicle fusionVesicular fusionComplex assemblySynaptic vesiclesFusion assayMolecular basisPhysiologically relevant conditionsPresynaptic calcium influxNeurotransmitter releaseVesiclesSNAREProteinMachineryCompetitive bindingFusion dynamicsComplexinExocytosisFusionCalcium influxOverlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles
Park D, Fujise K, Wu Y, Luján R, Del Olmo-Cabrera S, Wesseling J, De Camilli P. Overlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2409605121. PMID: 38985768, PMCID: PMC11260120, DOI: 10.1073/pnas.2409605121.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFibroblastsMembrane ProteinsMiceMice, KnockoutNerve Tissue ProteinsRatsSynapsinsSynaptic VesiclesSynaptogyrinsSynaptophysinConceptsSynaptic vesiclesFamily proteinsBiogenesis of synaptic vesiclesClusters of small vesiclesSize of synaptic vesiclesSynaptogyrin familySynaptogyrin-1Vesicle proteinsSynaptogyrinTransmembrane domainOrganismal levelSmall vesiclesProteinMild defectsVesiclesFamily membersBiogenesisSmall sizeFamilyMiceSynapsinCoexpressionAbundanceSynaptoporinMembersDual-Ring SNAREpin Machinery Tuning for Fast Synaptic Vesicle Fusion
Caruel M, Pincet F. Dual-Ring SNAREpin Machinery Tuning for Fast Synaptic Vesicle Fusion. Biomolecules 2024, 14: 600. PMID: 38786007, PMCID: PMC11117985, DOI: 10.3390/biom14050600.Peer-Reviewed Original Research
2023
Dose reduction in dynamic synaptic vesicle glycoprotein 2A PET imaging using artificial neural networks
Li A, Yang B, Naganawa M, Fontaine K, Toyonaga T, Carson R, Tang J. Dose reduction in dynamic synaptic vesicle glycoprotein 2A PET imaging using artificial neural networks. Physics In Medicine And Biology 2023, 68: 245006. PMID: 37857316, PMCID: PMC10739622, DOI: 10.1088/1361-6560/ad0535.Peer-Reviewed Original ResearchSynaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
Bera M, Radhakrishnan A, Coleman J, Sundaram R, Ramakrishnan S, Pincet F, Rothman J. Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2311484120. PMID: 37903271, PMCID: PMC10636311, DOI: 10.1073/pnas.2311484120.Peer-Reviewed Original ResearchConceptsSpecific molecular functionsSynaptic vesicle protein synaptophysinTarget membrane bilayerSensor synaptotagminSNARE proteinsMolecular functionsMembrane proteinsSNAREpinsReceptor vesiclesSingle-molecule measurementsGene knockoutMembrane bilayerLipid bilayersProtein synaptophysinVesiclesDetergent extractsHexamer structureSYPMechanism of actionProteinAssemblyChaperonesSynaptotagminExocytosisBilayersRoles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery
Sundaram R, Chatterjee A, Bera M, Grushin K, Panda A, Li F, Coleman J, Lee S, Ramakrishnan S, Ernst A, Gupta K, Rothman J, Krishnakumar S. Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2309516120. PMID: 37590407, PMCID: PMC10450444, DOI: 10.1073/pnas.2309516120.Peer-Reviewed Original ResearchMeSH KeywordsBlisterDiglyceridesExocytosisHumansSynaptic TransmissionSynaptic VesiclesSynaptotagminsConceptsCore protein machineryRelease-ready vesiclesSynaptic vesicle primingVesicle primingProtein machinerySingle-molecule imagingSNAREpin assemblyFunctional intermediatesFunctional reconstitutionMunc13DiacylglycerolCoordinated actionMunc18VesiclesMachineryComplete reconstitutionNew roleSelective effectDetailed characterizationChaperonesRate of caReconstitutionVAMP2ComplexinMutationsThe active zone protein CLA-1 (Clarinet) bridges two subsynaptic domains to regulate presynaptic sorting of ATG-9
Xuan Z, Colón-Ramos D. The active zone protein CLA-1 (Clarinet) bridges two subsynaptic domains to regulate presynaptic sorting of ATG-9. Autophagy 2023, 19: 2807-2808. PMID: 37389488, PMCID: PMC10472863, DOI: 10.1080/15548627.2023.2229227.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyCaenorhabditis elegansCarrier ProteinsPresynaptic TerminalsSynapsesSynaptic VesiclesConceptsATG-9Forward genetic screenAdaptor protein complexesIntegral synaptic vesicle proteinsActive zone proteinsSynaptic vesicle cycleCLA-1Synaptic vesicle proteinsGenetic screenPeriactive zoneAutophagosome biogenesisProtein complexesVesicle cycleVesicle proteinsLong isoformNovel roleSubsynaptic domainsZone proteinNeuronal synapsesSynaptic vesiclesProteinDistinct mechanismsVesiclesMutantsPresynaptic localizationDopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease
Vidyadhara D, Somayaji M, Wade N, Yücel B, Zhao H, Shashaank N, Ribaudo J, Gupta J, Lam T, Sames D, Greene L, Sulzer D, Chandra S. Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease. Cell Reports 2023, 42: 112231. PMID: 36920906, PMCID: PMC10127800, DOI: 10.1016/j.celrep.2023.112231.Peer-Reviewed Original ResearchConceptsParkinson's diseaseMotor deficitsDopamine transporterPathogenesis of PDNigral dopaminergic lossProgressive motor deficitsΑ-synuclein pathologyEarly-onset Parkinson's diseaseDopamine sequestrationDopaminergic vulnerabilityDopaminergic lossKO micePresynaptic sitesKO brainNeurochemical analysisDorsal striatumKnockout miceCardinal featuresReuptake kineticsL-DOPADiseaseSynaptic autophagyFunction mutationsDeficitsMiceSynaptic 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 terminalsClusters
2022
Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion
Zhu J, McDargh ZA, Li F, Krishnakumar SS, Rothman JE, O’Shaughnessy B. Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208337119. PMID: 36103579, PMCID: PMC9499556, DOI: 10.1073/pnas.2208337119.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCalciumPhosphatidylinositol 4,5-DiphosphateSynaptic VesiclesSynaptotagmin IConceptsVesicle dockingPlasma membrane domainsSynaptic vesiclesCalcium sensor synaptotagminSynaptic vesicle dockingInhibitor of fusionFusion clampSensor synaptotagminMembrane domainsTrigger fusionPlasma membraneC2AB domainAnionic phospholipid bilayersNeuronal synapsesMembrane compositionPhospholipid monolayersATP levelsVesiclesExocytotic releaseDockingPhospholipid bilayersMultimodal imaging of synaptic vesicles with a single probe
An SJ, Stagi M, Gould TJ, Wu Y, Mlodzianoski M, Rivera-Molina F, Toomre D, Strittmatter SM, De Camilli P, Bewersdorf J, Zenisek D. Multimodal imaging of synaptic vesicles with a single probe. Cell Reports Methods 2022, 2: 100199. PMID: 35497490, PMCID: PMC9046237, DOI: 10.1016/j.crmeth.2022.100199.Peer-Reviewed Original ResearchConceptsC2 domainSynaptic vesiclesSynaptic vesicle recyclingMembrane-binding C2 domainMultiple microscopy methodsEndocytic markersMembrane recyclingVesicle functionVesicle populationsCytosolic phospholipase ACell typesPhospholipase ADetectable tagMicroscopy modalitiesModular probesMultiple microscopy techniquesVesiclesComplete understandingDomainMicroscopy methodsMultiple levelsProbeAvailable probesMicroscopy techniquesPathwayMolecular determinants of complexin clamping and activation function
Bera M, Ramakrishnan S, Coleman J, Krishnakumar SS, Rothman JE. Molecular determinants of complexin clamping and activation function. ELife 2022, 11: e71938. PMID: 35442188, PMCID: PMC9020821, DOI: 10.7554/elife.71938.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportCalciumConstrictionMembrane FusionNerve Tissue ProteinsSNARE ProteinsSynaptic VesiclesConceptsSynaptotagmin-1Single-vesicle fusionAccessory helixFusion clampHelical domainMolecular detailsComplexinMutational analysisVesicle releaseFusion kineticsMolecular determinantsSpecific interactionsInhibitory functionProbability of fusionRapid CaSNAREpinsAssembly processFusionClamping functionDomainHelixVesiclesFunctionMembraneInteractionPresynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9
Yang S, Park D, Manning L, Hill SE, Cao M, Xuan Z, Gonzalez I, Dong Y, Clark B, Shao L, Okeke I, Almoril-Porras A, Bai J, De Camilli P, Colón-Ramos DA. Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9. Neuron 2022, 110: 824-840.e10. PMID: 35065714, PMCID: PMC9017068, DOI: 10.1016/j.neuron.2021.12.031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyAutophagy-Related ProteinsCaenorhabditis elegansEndocytosisPresynaptic TerminalsSynaptic VesiclesConceptsSynaptic vesicle cycleVesicle cyclePresynaptic autophagyAutophagosome biogenesisATG-9Only transmembrane proteinTrans-Golgi networkCellular degradation pathwayPresynaptic sitesActivity-dependent mannerTransmembrane proteinSynaptojanin 1Synaptic fociBiogenesisAutophagyNeuronal healthDegradation pathwayTraffickingPathwayParkinson's diseaseSynaptic activityNeuronal activityElegansSitesEndocytosis
2021
Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans
Angarita GA, Worhunsky PD, Naganawa M, Toyonaga T, Nabulsi NB, Li C, Esterlis I, Skosnik PD, Radhakrishnan R, Pittman B, Gueorguieva R, Potenza MN, Finnema SJ, Huang Y, Carson RE, Malison RT. Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans. Addiction Biology 2021, 27: e13123. PMID: 34852401, PMCID: PMC8891080, DOI: 10.1111/adb.13123.Peer-Reviewed Original ResearchMeSH KeywordsBrainCocaineHumansNerve Tissue ProteinsPositron-Emission TomographyPrefrontal CortexPyridinesSynaptic VesiclesConceptsCocaine use disorderAnterior cingulate cortexRecent cocaine useSynaptic densityMedial orbitofrontal cortexPrefrontal cortexCocaine useOrbitofrontal cortexUse disordersVentromedial prefrontal cortexPositron emission tomography scanPositron emission tomography studyEmission tomography scanSynaptic vesicle glycoprotein 2AHealthy control subjectsVolume of distributionEmission tomography studiesAcute cocaineControl subjectsTomography scanCocaine exposurePreclinical studiesHC subjectsDendritic spinesLifetime cocaine useA metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16
Zheng C, Holden D, Zheng MQ, Pracitto R, Wilcox KC, Lindemann M, Felchner Z, Zhang L, Tong J, Fowles K, Finnema SJ, Nabulsi N, Carson RE, Huang Y, Cai Z. A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 49: 1482-1496. PMID: 34761284, PMCID: PMC8940841, DOI: 10.1007/s00259-021-05597-5.Peer-Reviewed Original ResearchMeSH KeywordsAminoacridinesAnimalsBrainHumansMembrane GlycoproteinsPositron-Emission TomographyRadiopharmaceuticalsSynaptic VesiclesConceptsTest-retest variabilityVolume of distributionCentral nervous systemTime-activity curvesPET tracersCentrum semiovaleSynaptic vesicle protein 2AAbsolute test-retest variabilityWhole central nervous systemNonhuman primate brainPlasma free fractionBrain PET scansHigh specific bindingSpecific bindingNondisplaceable volumePlasma input functionNHP brainOne-tissue compartment modelArterial bloodRegional time-activity curvesPET scansNervous systemPrimate brainMonkey brainPreclinical characterizationAn open-access volume electron microscopy atlas of whole cells and tissues
Xu CS, Pang S, Shtengel G, Müller A, Ritter AT, Hoffman HK, Takemura SY, Lu Z, Pasolli HA, Iyer N, Chung J, Bennett D, Weigel AV, Freeman M, van Engelenburg SB, Walther TC, Farese RV, Lippincott-Schwartz J, Mellman I, Solimena M, Hess HF. An open-access volume electron microscopy atlas of whole cells and tissues. Nature 2021, 599: 147-151. PMID: 34616045, PMCID: PMC9004664, DOI: 10.1038/s41586-021-03992-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDatasets as TopicDrosophila melanogasterFemaleGolgi ApparatusHumansInformation DisseminationInterphaseIslets of LangerhansMaleMiceMicroscopy, Electron, ScanningMicrotubulesNeurogliaNeuronsOpen Access PublishingOrganellesOvarian NeoplasmsRibosomesSynaptic VesiclesT-Lymphocytes, CytotoxicConceptsDrosophila neural tissueWhole cellsThin-section electron microscopyVolume electron microscopyCellular architectureMouse pancreatic isletsCancer cellsEM tomographyCellular structureCellsCellular samplesNeural tissuePancreatic isletsEnhanced signal detectionAtlasBeam-scanning electron microscopyTissueElectron microscopyOpen access dataBiologyImmune cellsSubsequent analysisSEM scanningMicroscopyVesicle capture by membrane‐bound Munc13‐1 requires self‐assembly into discrete clusters
Li F, Sundaram R, Gatta AT, Coleman J, Ramakrishnan S, Krishnakumar SS, Pincet F, Rothman JE. Vesicle capture by membrane‐bound Munc13‐1 requires self‐assembly into discrete clusters. FEBS Letters 2021, 595: 2185-2196. PMID: 34227103, DOI: 10.1002/1873-3468.14157.Peer-Reviewed Original ResearchMeSH KeywordsCell MembraneHEK293 CellsHumansLipid BilayersNerve Tissue ProteinsProtein DomainsSynaptic VesiclesConceptsMunc13-1Vesicle captureSpecific plasma membrane domainsStep-wise photobleachingC-domainMunc13-1 proteinPlasma membrane domainsSynaptic vesicle dockingC-terminal CVesicle dockingMembrane domainsTIRF microscopySoluble proteinVesicle membraneActive zoneMultiple copiesSynaptic vesiclesFunctional significanceSmall unilamellar vesiclesLipid bilayersVesiclesUnilamellar vesiclesProteinDiscrete clustersCopiesIn vivo evidence of lower synaptic vesicle density in schizophrenia
Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, Hillmer AT, Esterlis I, Huang Y, Nabulsi N, Carson RE, D’Souza D. In vivo evidence of lower synaptic vesicle density in schizophrenia. Molecular Psychiatry 2021, 26: 7690-7698. PMID: 34135473, DOI: 10.1038/s41380-021-01184-0.Peer-Reviewed Original ResearchMeSH KeywordsBrainHumansNerve Tissue ProteinsPositron-Emission TomographySchizophreniaSynaptic VesiclesConceptsSynaptic vesicle densityHealthy controlsVesicle densityHigh-resolution research tomographySynaptic densitySCZ patientsVivo measuresNovel positron emission tomography (PET) ligandGender-matched healthy controlsCumulative antipsychotic exposurePositron emission tomography (PET) ligandSynaptic spine densityPsychosis symptom severityGray matter volumeJ bindingAntipsychotic exposureSpine densityDisease progressionFrontal cortexOccipital cortexTomography ligandTemporal cortexAnterior cingulateVivo findingsParietal cortexTranscriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
Jimenez‐Marin A, Diez I, Labayru G, Sistiaga A, Caballero M, Andres‐Benito P, Sepulcre J, Ferrer I, de Munain A, Cortes J. Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration. Neuropathology And Applied Neurobiology 2021, 47: 1092-1108. PMID: 33955002, PMCID: PMC9292638, DOI: 10.1111/nan.12725.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlzheimer DiseaseBrainCentral Nervous SystemDystrophinFemaleHumansMaleMiddle AgedMyotonic DystrophySynaptic Vesiclestau ProteinsConceptsMicrotubule-associated protein tauAllen Human Brain AtlasRNA analysisSynaptic vesicle recyclingSynaptic vesicle genesHypothesis-driven genesGene clusterDopamine neurotransmitter pathwaysVesicle recyclingProtein tauTranscriptome mapTranscriptome interactionsTau pathologyMyotonic dystrophy type IBrain degenerationBiological processesGenesHuman Brain AtlasAlzheimer's diseaseTranscriptional signatureNeurobiological mechanismsCognitive functionAlpha-synucleinNeurotransmitter pathwaysRNA
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