2023
The 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 synapsesBindingPlasticitySynaptotagminSnareVesicles
2019
Structural basis for the clamping and Ca2+ activation of SNARE-mediated fusion by synaptotagmin
Grushin K, Wang J, Coleman J, Rothman JE, Sindelar CV, Krishnakumar SS. Structural basis for the clamping and Ca2+ activation of SNARE-mediated fusion by synaptotagmin. Nature Communications 2019, 10: 2413. PMID: 31160571, PMCID: PMC6546687, DOI: 10.1038/s41467-019-10391-x.Peer-Reviewed Original ResearchConceptsCryo-electron microscopy structureActivation of SNAREsDependent membrane interactionsAnionic lipid headgroupsFusion clampActivator functionSNARE bundleSNARE proteinsMicroscopy structureC2B domainStructural basisSynaptotagmin-1SNAREpinsAliphatic loopsMembrane interactionsComplete assemblyLipid headgroupsLipid membranesNeurotransmitter releaseMembraneKey determinantSynaptotagminSyt1Calcium influxPartial insertionMechanisms of Neurological Dysfunction in GOSR2 Progressive Myoclonus Epilepsy, a Golgi SNAREopathy
Jepson JEC, Praschberger R, Krishnakumar SS. Mechanisms of Neurological Dysfunction in GOSR2 Progressive Myoclonus Epilepsy, a Golgi SNAREopathy. Neuroscience 2019, 420: 41-49. PMID: 30954670, DOI: 10.1016/j.neuroscience.2019.03.057.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumSNARE proteinsProgressive myoclonus epilepsySecretory trafficking pathwaysCis-Golgi membranesMis-sense mutationsTransport vesiclesGolgi transportTrafficking pathwaysVesicles budSecretory pathwaySuccessive fusion eventsTarget membraneFusion eventsEssential functionsDevelopmental defectsMolecular mechanismsMyoclonus epilepsyProteinFusion stepSevere neurological disordersMutationsMembranePathwayInitial step
2018
PRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly
Coleman J, Jouannot O, Ramakrishnan SK, Zanetti MN, Wang J, Salpietro V, Houlden H, Rothman JE, Krishnakumar SS. PRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly. Cell Reports 2018, 22: 820-831. PMID: 29346777, PMCID: PMC5792450, DOI: 10.1016/j.celrep.2017.12.056.Peer-Reviewed Original ResearchConceptsProline-rich transmembrane protein 2SNARE complex assemblyComplex assemblyTrans-SNARE complex assemblyTerminal proline-rich domainSynaptic SNARE proteinsProline-rich domainParoxysmal neurological disordersSynaptic vesicle primingLive-cell imagingTransmembrane protein 2Synaptic fusionSNARE proteinsVesicle primingSingle exocytotic eventsBiophysical analysisFusion assaysMolecular mechanismsFunction mutationsPhysiological roleExocytotic eventsPre-synaptic terminalsPC12 cellsProtein 2Single vesicles
2016
Using ApoE Nanolipoprotein Particles To Analyze SNARE-Induced Fusion Pores
Bello OD, Auclair SM, Rothman JE, Krishnakumar SS. Using ApoE Nanolipoprotein Particles To Analyze SNARE-Induced Fusion Pores. Langmuir 2016, 32: 3015-3023. PMID: 26972604, PMCID: PMC4946868, DOI: 10.1021/acs.langmuir.6b00245.Peer-Reviewed Original ResearchMeSH KeywordsApolipoproteins ECalciumCholesterolDextransDimyristoylphosphatidylcholineDithioniteFluorescent DyesLiposomesMembrane FusionNanoparticlesParticle SizePhosphatidylcholinesPhosphatidylethanolaminesPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositolsPhosphatidylserinesSynaptosomal-Associated Protein 25Syntaxin 1Vesicle-Associated Membrane Protein 2