2019
Mechanisms 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
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 controlPHluorinSyt1SYTPRRT2 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
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 tweezersComplexes