2020
Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly
Sundaram R, Jin H, Li F, Shu T, Coleman J, Yang J, Pincet F, Zhang Y, Rothman JE, Krishnakumar SS. Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly. FEBS Letters 2020, 595: 297-309. PMID: 33222163, PMCID: PMC8068094, DOI: 10.1002/1873-3468.14006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCloning, MolecularEscherichia coliGene ExpressionGenetic VectorsLipid BilayersLiposomesMiceModels, MolecularNerve Tissue ProteinsOptical TweezersPhosphatidylcholinesPhosphatidylethanolaminesPhosphatidylserinesPolyethylene GlycolsProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant Fusion ProteinsSynaptosomal-Associated Protein 25Syntaxin 1Vesicle-Associated Membrane Protein 2ConceptsSNARE complex assemblyComplex assemblyMunc13-1 MUN domainDetailed structure-function analysisSNARE protein VAMP2Syntaxin 1/Structure-function analysisSynaptic vesicle fusionOptical tweezers studiesSNARE assemblySNARE motifMUN domainMunc18-1Syntaxin-1Munc13-1FRET spectroscopyLinker regionVesicle fusionDirect bindingPhospholipid bilayersPresynaptic membraneSNAP25AssemblyBindingRecruitsSynergistic 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 roleFusionExocytosisMachineryProteinBindsMechanism
2019
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
Salpietro V, Malintan NT, Llano-Rivas I, Spaeth CG, Efthymiou S, Striano P, Vandrovcova J, Cutrupi MC, Chimenz R, David E, Di Rosa G, Marce-Grau A, Raspall-Chaure M, Martin-Hernandez E, Zara F, Minetti C, Study D, Group S, Salpietro V, Efthymiou S, Kriouile Y, Khorassani M, Aguennouz M, Karashova B, Avdjieva D, Kathom H, Tincheva R, Van Maldergem L, Nachbauer W, Boesch S, Arning L, Timmann D, Cormand B, Pérez-Dueñas B, Di Rosa G, Pironti E, Goraya J, Sultan T, Kirmani S, Ibrahim S, Jan F, Mine J, Banu S, Veggiotti P, Ferrari M, Verrotti A, Marseglia G, Savasta S, Garavaglia B, Scuderi C, Borgione E, Dipasquale V, Cutrupi M, Portaro S, Sanchez B, Pineda-Marfa’ M, Munell F, Macaya A, Boles R, Heimer G, Papacostas S, Manole A, Malintan N, Zanetti M, Hanna M, Rothman J, Kullmann D, Houlden H, Bello O, De Zorzi R, Fortuna S, Dauber A, Alkhawaja M, Sultan T, Mankad K, Vitobello A, Thomas Q, Mau-Them F, Faivre L, Martinez-Azorin F, Prada C, Macaya A, Kullmann D, Rothman J, Krishnakumar S, Houlden H. Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment. American Journal Of Human Genetics 2019, 104: 721-730. PMID: 30929742, PMCID: PMC6451933, DOI: 10.1016/j.ajhg.2019.02.016.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAutistic DisorderBrainChildChild, PreschoolEpilepsyExocytosisFemaleHeterozygoteHumansIntellectual DisabilityLipidsMagnetic Resonance ImagingMaleMembrane FusionMovement DisordersMuscle HypotoniaMutationNeurodevelopmental DisordersNeuronsNeurotransmitter AgentsPhenotypeProtein DomainsR-SNARE ProteinsSynapsesVesicle-Associated Membrane Protein 2ConceptsNon-synonymous variantsDe novo mutationsSNARE protein VAMP2Synaptic membrane fusionC-terminal regionNovo mutationsSNARE motifSynaptosomal-associated protein 25C-terminusMembrane fusionVAMP2Vesicle fusionHuman brain developmentAcid deletionSynaptic vesiclesVesicular exocytosisHeterozygous de novo mutationsProtein 25Hyperkinetic movement disordersAdditional neurological featuresHuman neurodevelopmentCentral visual impairmentDisease mechanismsUnrelated individualsMutations
2017
Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
Michalski N, Goutman JD, Auclair SM, de Monvel J, Tertrais M, Emptoz A, Parrin A, Nouaille S, Guillon M, Sachse M, Ciric D, Bahloul A, Hardelin JP, Sutton RB, Avan P, Krishnakumar SS, Rothman JE, Dulon D, Safieddine S, Petit C. Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses. ELife 2017, 6: e31013. PMID: 29111973, PMCID: PMC5700815, DOI: 10.7554/elife.31013.Peer-Reviewed Original ResearchConceptsVesicle fusionVesicle pool replenishmentIHC active zonesInner hair cellsPresynaptic plasma membraneSynaptic vesicle cycleMembrane capacitance measurementsRole of otoferlinAuditory brainstem response wavesTransmembrane proteinVesicle cycleSynaptic exocytosisPlasma membraneVoltage-gated CaHair cell ribbonC-domainSynaptic vesiclesOtoferlinSynaptic CaSensory cellsSynapse structureIntracellular CaNeurotransmitter releaseMutant miceRibbon synapses