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 roleFusionExocytosisMachineryProteinBindsMechanismSynaptotagmin 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
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 insertionSynaptotagmin oligomers are necessary and can be sufficient to form a Ca2+‐sensitive fusion clamp
Ramakrishnan S, Bera M, Coleman J, Krishnakumar SS, Pincet F, Rothman JE. Synaptotagmin oligomers are necessary and can be sufficient to form a Ca2+‐sensitive fusion clamp. FEBS Letters 2019, 593: 154-162. PMID: 30570144, PMCID: PMC6349546, DOI: 10.1002/1873-3468.13317.Peer-Reviewed Original Research
2018
Synaptotagmin 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 controlPHluorinSyt1SYTRearrangements under confinement lead to increased binding energy of Synaptotagmin‐1 with anionic membranes in Mg2+ and Ca2+
Gruget C, Coleman J, Bello O, Krishnakumar SS, Perez E, Rothman JE, Pincet F, Donaldson SH. Rearrangements under confinement lead to increased binding energy of Synaptotagmin‐1 with anionic membranes in Mg2+ and Ca2+. FEBS Letters 2018, 592: 1497-1506. PMID: 29578584, DOI: 10.1002/1873-3468.13040.Peer-Reviewed Original ResearchMeSH KeywordsCalciumCell MembraneDose-Response Relationship, DrugMagnesiumProtein BindingSurface PropertiesSynaptotagmin IThermodynamics
2014
Calcium sensitive ring-like oligomers formed by synaptotagmin
Wang J, Bello O, Auclair SM, Wang J, Coleman J, Pincet F, Krishnakumar SS, Sindelar CV, Rothman JE. Calcium sensitive ring-like oligomers formed by synaptotagmin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 13966-13971. PMID: 25201968, PMCID: PMC4183308, DOI: 10.1073/pnas.1415849111.Peer-Reviewed Original ResearchMeSH KeywordsCalciumHumansLipid BilayersMultiprotein ComplexesProtein Structure, TertiarySNARE ProteinsSynaptotagmin IConceptsSynaptic vesicle protein Synaptotagmin 1Cytosolic domainSoluble N-ethylmaleimide-sensitive factorN-ethylmaleimide-sensitive factorMembrane fusion machineryReceptor complex assemblyRing-like oligomersFusion machineryC2 domainComplex assemblySynaptotagmin-1Helical reconstructionFusion proceedsNovel mechanismStructural mechanismsLipid monolayersNeurotransmitter releaseAbsence of calciumPhysiological concentrationsRing formationPresence of calciumFree calcium ionsSynaptotagminCalcium influxCircular arrangement