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
2020
Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
Tagliatti E, Bello OD, Mendonça PRF, Kotzadimitriou D, Nicholson E, Coleman J, Timofeeva Y, Rothman JE, Krishnakumar SS, Volynski KE. Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 3819-3827. PMID: 32015138, PMCID: PMC7035618, DOI: 10.1073/pnas.1920403117.Peer-Reviewed Original Research
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 synapsesMutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity
Praschberger R, Lowe SA, Malintan NT, Giachello CNG, Patel N, Houlden H, Kullmann DM, Baines RA, Usowicz MM, Krishnakumar SS, Hodge JJL, Rothman JE, Jepson JEC. Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity. Cell Reports 2017, 21: 97-109. PMID: 28978487, PMCID: PMC5640804, DOI: 10.1016/j.celrep.2017.09.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDendritesDrosophila melanogasterFemaleFibroblastsGene ExpressionGenetic Association StudiesGolgi ApparatusHumansMaleMembrane FusionMutationMyoclonic Epilepsies, ProgressivePhenotypePrimary Cell CultureQb-SNARE ProteinsRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSecretory PathwaySynapsesYoung AdultConceptsMembrane fusionGolgi membrane fusionProgressive myoclonus epilepsyGenotype-phenotype relationshipsPresynaptic cytoskeletonEssential proteinsDrosophila modelMembrinMutationsPathogenic mutationsSynaptic functionProteinMyoclonus epilepsyExplanatory basisCytoskeletonGrowthSynaptic integrityPathway deficitsNervous systemMulti-layered strategySnareFusionFragmentation