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 ResearchConceptsSynaptic 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 influx
2023
Synaptophysin 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 actionProteinAssemblyChaperonesSynaptotagminExocytosisBilayersThe release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses
Norman C, Krishnakumar S, Timofeeva Y, Volynski K. The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses. Communications Biology 2023, 6: 1091. PMID: 37891212, PMCID: PMC10611806, DOI: 10.1038/s42003-023-05445-2.Peer-Reviewed Original ResearchConceptsFusion clampSV exocytosisSynaptic vesiclesNeurotransmitter releaseSNARE complexSNARE proteinsSV fusionPhysiological timescalesSynaptotagmin-1Synergistic regulationMolecular biochemistryComplete assemblyPresynaptic proteinsSynaptotagmin-7Molecular architectureCalcium bindingExocytosisDual bindingProteinCentral synapsesBindingPlasticitySynaptotagminSnareVesiclesUse of Ecto-Tagged Integrins to Monitor Integrin Exocytosis and Endocytosis
Huet-Calderwood C, Rivera-Molina F, Toomre D, Calderwood D. Use of Ecto-Tagged Integrins to Monitor Integrin Exocytosis and Endocytosis. Methods In Molecular Biology 2023, 2608: 17-38. PMID: 36653699, PMCID: PMC9999384, DOI: 10.1007/978-1-0716-2887-4_2.ChaptersConceptsΒ1 integrinTotal internal reflection fluorescence microscopyNormal cell adhesionIntegrin adhesion receptorsReflection fluorescence microscopyAdhesion receptorsCell adhesionEndocytosisFluorescence microscopyExocytosisIntegrinsCellsHaloTagPHluorinIntracellular labelingEctoPhotobleachingTagsReceptorsChaseFluorescentAdhesionLabelingMigration
2022
Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis
An S, Anneken A, Xi Z, Choi C, Schlessinger J, Toomre D. Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208947119. PMID: 36417441, PMCID: PMC9860279, DOI: 10.1073/pnas.2208947119.Peer-Reviewed Original ResearchConceptsPI-3K/Akt pathwayAkt pathwayAkt activationDocking protein Gab1EGF-stimulated activationEpithelial cellsLive-cell imagingPhosphoinositide-3 kinaseCell survival pathwaysExocyst complexExocyst functionSmall molecule inhibitorsVesicle tethersExocytic fusionProtein Gab1EGF stimulationExocystSurvival pathwaysExocytosisInhibitors resultsPathwayImportant pathwayEGFR inhibitionMinute time scaleVesiclesInhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes
Meriin AB, Zaarur N, Bogan JS, Kandror KV. Inhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes. Scientific Reports 2022, 12: 15640. PMID: 36123369, PMCID: PMC9485115, DOI: 10.1038/s41598-022-19534-5.Peer-Reviewed Original ResearchConceptsInhibitors of RNAGLUT4 translocationProtein synthesisEndocytosis of GLUT4Glucose uptakeRecycling of transferrinGlucose transporter 4Actinomycin DBiosynthesis de novoSignaling proteinsPlasma membraneTransporter 4Intracellular retentionContinuous RNATranslocationRNADe novoAdipocytesVesiclesInhibitorsTBC1D4UptakeEndocytosisGLUT4ExocytosisExtracellular Vesicles Mediate the Intercellular Exchange of Nanoparticles
Wu X, Tang T, Wei Y, Cummins K, Wood D, Pang H. Extracellular Vesicles Mediate the Intercellular Exchange of Nanoparticles. Advanced Science 2022, 9: 2102441. PMID: 35243822, PMCID: PMC8895114, DOI: 10.1002/advs.202102441.Peer-Reviewed Original ResearchConceptsIntercellular exchangeExtracellular vesiclesComplex tissuesImportance of EVsCell-cell contactTranscellular transport routeDirect cell-cell contactSubcellular transportNP endocytosisExocytosisAccumulative evidenceVesiclesSame receptorCrucial rolePotential mechanismsCellsTransport routesEndocytosisTissueSignificant fractionTransportVitroAssaysVivoReceptorsRapid propagation of membrane tension at retinal bipolar neuron presynaptic terminals
Perez C, Dudzinski NR, Rouches M, Landajuela A, Machta B, Zenisek D, Karatekin E. Rapid propagation of membrane tension at retinal bipolar neuron presynaptic terminals. Science Advances 2022, 8: eabl4411. PMID: 34985955, PMCID: PMC11580022, DOI: 10.1126/sciadv.abl4411.Peer-Reviewed Original ResearchMembrane tensionMembrane flowStimulation of exocytosisSynaptic vesicle turnoverNeuroendocrine adrenal chromaffin cellsCell divisionVesicle turnoverCellular activitiesCell migrationCell typesAdrenal chromaffin cellsChromaffin cellsGlobal decreasePresynaptic terminalsRapid propagationEndocytosisExocytosisNeuronal terminalsPhagocytosisTurnoverGradientCellsDivisionMigration
2020
Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
Ramakrishnan S, Bera M, Coleman J, Rothman JE, Krishnakumar SS. Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis. ELife 2020, 9: e54506. PMID: 32401194, PMCID: PMC7220375, DOI: 10.7554/elife.54506.Peer-Reviewed Original ResearchConceptsSynaptotagmin-1Vesicular fusion machinerySingle-vesicle fusionFusion of vesiclesSNARE complexFusion machineryNeuronal exocytosisOligomer bindsRegulatory proteinsVesicle fusionSNAREpinsSynchronous fusionSynaptic vesiclesNovel mechanismVesiclesComplexinKinetic delayPrimary interfaceSynergistic roleFusionExocytosisMachineryProteinBindsMechanismDynamin Function in Exocytosis and Endocytosis Coupling of Dense-Core Vesicles in Pancreatic Beta Cells
Fan F, Wendlick J, Tamarina N, Wu Y, Ferguson S, Philipson L, De Camilli P, Lou X. Dynamin Function in Exocytosis and Endocytosis Coupling of Dense-Core Vesicles in Pancreatic Beta Cells. Biophysical Journal 2020, 118: 488a. DOI: 10.1016/j.bpj.2019.11.2700.Peer-Reviewed Original Research
2019
Symmetrical organization of proteins under docked synaptic vesicles
Li X, Radhakrishnan A, Grushin K, Kasula R, Chaudhuri A, Gomathinayagam S, Krishnakumar SS, Liu J, Rothman JE. Symmetrical organization of proteins under docked synaptic vesicles. FEBS Letters 2019, 593: 144-153. PMID: 30561792, PMCID: PMC6353562, DOI: 10.1002/1873-3468.13316.Peer-Reviewed Original ResearchConceptsCryo-electron tomography analysisSymmetrical organizationCalcium-regulated exocytosisMunc18 proteinsProtein machineryFusion machinerySingle SNAREpinCircular oligomersMutational analysisRadial positioningSynaptic vesiclesRelease machineryMachinerySynaptotagminProteinRing hypothesisVesiclesObserved arrangementUnderlying mechanismSNAREpinsComplexinNerve growthExocytosisGrowth
2018
Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones
Vysokov NV, Silva JP, Lelianova VG, Suckling J, Cassidy J, Blackburn JK, Yankova N, Djamgoz MB, Kozlov SV, Tonevitsky AG, Ushkaryov YA. Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones. ELife 2018, 7: e37935. PMID: 30457553, PMCID: PMC6245728, DOI: 10.7554/elife.37935.Peer-Reviewed Original ResearchConceptsLatrophilin-1Axonal growth conesAxonal attractionAdhesion G protein-coupled receptorsPostsynaptic transmembrane proteinsG protein-coupled receptorsGrowth conesTrans-synaptic interactionsGrowth cone steeringRegulated proteolysisTransmembrane proteinDownstream signalingAxonal pathfindingNeuronal developmentEnhanced exocytosisNovel mechanismSynapse formationNeurite outgrowthTeneurinsIntercellular spacesCytosolic calciumStable gradientSynaptogenesisExocytosisSignalingSynaptotagmin oligomerization is essential for calcium control of regulated exocytosis
Bello OD, Jouannot O, Chaudhuri A, Stroeva E, Coleman J, Volynski KE, Rothman JE, Krishnakumar SS. Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e7624-e7631. PMID: 30038018, PMCID: PMC6094142, DOI: 10.1073/pnas.1808792115.Peer-Reviewed Original ResearchConceptsRegulated exocytosisFusion machineryC2 domain proteinsCore fusion machinerySingle vesicle exocytosisConstitutive exocytosisPrincipal CaVesicular releaseMolecular mechanismsSensitive oligomersExocytosisPheochromocytoma cellsSelective disruptionSpontaneous fusionCritical roleMachineryOligomerizationDirect activationCentral componentStructural featuresConsiderable insightCalcium controlPHluorinSyt1SYTA liquid phase of synapsin and lipid vesicles
Milovanovic D, Wu Y, Bian X, De Camilli P. A liquid phase of synapsin and lipid vesicles. Science 2018, 361: 604-607. PMID: 29976799, PMCID: PMC6191856, DOI: 10.1126/science.aat5671.Peer-Reviewed Original ResearchConceptsSynaptic vesiclesNeurotransmitter-containing synaptic vesiclesCalmodulin-dependent protein kinase IILipid vesiclesCalcium/calmodulin-dependent protein kinase IIProtein kinase IISmall lipid vesiclesKinase IILiquid-liquid phase separationSynapsinDistinct liquid phasesVesiclesTight clusterSynapsin 1Presynaptic sitesPhosphorylationExocytosis
2017
Two Disease-Causing SNAP-25B Mutations Selectively Impair SNARE C-terminal Assembly
Rebane AA, Wang B, Ma L, Qu H, Coleman J, Krishnakumar S, Rothman JE, Zhang Y. Two Disease-Causing SNAP-25B Mutations Selectively Impair SNARE C-terminal Assembly. Journal Of Molecular Biology 2017, 430: 479-490. PMID: 29056461, PMCID: PMC5805579, DOI: 10.1016/j.jmb.2017.10.012.Peer-Reviewed Original ResearchConceptsSoluble N-ethylmaleimide-sensitive factor attachment receptorSNARE assemblySynaptic exocytosisMembrane fusionSingle-molecule optical tweezersT-SNARE complexVesicle-associated SNAREsTarget plasma membraneC-terminal assemblyFour-helix bundleC-terminal regionSNARE complexPlasma membraneMolecular mechanismsZipperingMutationsNumerous diseasesAssembly energyNeurotransmitter releaseExocytosisAttachment receptorAssemblyNeurological disordersOptical tweezersComplexesNovel ecto-tagged integrins reveal their trafficking in live cells
Huet-Calderwood C, Rivera-Molina F, Iwamoto DV, Kromann EB, Toomre D, Calderwood DA. Novel ecto-tagged integrins reveal their trafficking in live cells. Nature Communications 2017, 8: 570. PMID: 28924207, PMCID: PMC5603536, DOI: 10.1038/s41467-017-00646-w.Peer-Reviewed Original ResearchConceptsIntegrin functionΒ1 integrinLive cellsCell surface adhesion receptorsHeterodimeric cell-surface adhesion receptorsIntegrin endocytosisMulticellular organismsNovel powerful toolFocal adhesionsKnockout fibroblastsIntegrin activationAdhesion receptorsExtracellular loopIntegrinsTraffickingMajor mysteriesCellsTagsAdhesionHaloTagEndocytosisPowerful toolExocytosisOrganismsVesiclesExcess cholesterol inhibits glucose‐stimulated fusion pore dynamics in insulin exocytosis
Xu Y, Toomre DK, Bogan JS, Hao M. Excess cholesterol inhibits glucose‐stimulated fusion pore dynamics in insulin exocytosis. Journal Of Cellular And Molecular Medicine 2017, 21: 2950-2962. PMID: 28544529, PMCID: PMC5661106, DOI: 10.1111/jcmm.13207.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell MembraneCholesterolDiabetes Mellitus, Type 2DynaminsExocytosisGene Expression RegulationGlucoseHumansInsulinInsulin-Secreting CellsMembrane FusionMiceMicroscopy, FluorescenceModels, BiologicalPhosphatidylinositol 4,5-DiphosphateSecretory VesiclesSignal TransductionConceptsFusion pore dynamicsInsulin exocytosisFusion eventsPore dynamicsGlucose-triggered insulin secretionΒ-cellsFull fusionSingle granule levelTotal internal reflection fluorescence microscopySingle exocytic eventsReflection fluorescence microscopyImpairs β-cell functionExcess cholesterolGTPase dynaminExocytic eventsRole of cholesterolPlasma membranePancreatic β-cellsMolecular mechanismsInsulin granulesCompound exocytosisFusion kineticsΒ-cell dysfunctionExocytosisType 2 diabetes
2016
Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels
Lv C, Stewart WJ, Akanyeti O, Frederick C, Zhu J, Santos-Sacchi J, Sheets L, Liao JC, Zenisek D. Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels. Cell Reports 2016, 15: 2784-2795. PMID: 27292637, PMCID: PMC5334794, DOI: 10.1016/j.celrep.2016.05.045.Peer-Reviewed Original ResearchConceptsNeuromast hair cellsProper synaptic localizationHair cellsSynaptic ribbonsZebrafish genesProper localizationCalcium channelsSynaptic vesiclesSmall vesiclesEnhanced exocytosisFrameshift mutationRibeye proteinsSynaptic localizationVesiclesRelease sitesCellsRibeyeRibbon-like structuresNon-spiking cellsSensory systemsLocalizationGenesExocytosisSimilar numberProteinComplexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses
Mortensen LS, Park SJ, Ke JB, Cooper BH, Zhang L, Imig C, Löwel S, Reim K, Brose N, Demb JB, Rhee JS, Singer JH. Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses. Cell Reports 2016, 15: 2239-2250. PMID: 27239031, PMCID: PMC5134263, DOI: 10.1016/j.celrep.2016.05.012.Peer-Reviewed Original ResearchConceptsRod bipolarsAsynchronous releaseAmacrine cell synapsesRetinal ganglion cellsRetinal pathwaysGanglion cellsCell synapsesRetinal circuitsRibbon synapsesMouse retinaMultivesicular releaseNeural circuitsComplexin proteinsSynapsesCircuit functionCplx3SignalingStudy linksReleaseExocytosisRB outputRetina
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