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 membraneSNAP25AssemblyBindingRecruits
2017
Mutations 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 strategySnareFusionFragmentationCircular oligomerization is an intrinsic property of synaptotagmin
Wang J, Li F, Bello OD, Sindelar CV, Pincet F, Krishnakumar SS, Rothman JE. Circular oligomerization is an intrinsic property of synaptotagmin. ELife 2017, 6: e27441. PMID: 28850328, PMCID: PMC5576491, DOI: 10.7554/elife.27441.Peer-Reviewed Original ResearchKv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
Vivekananda U, Novak P, Bello OD, Korchev YE, Krishnakumar SS, Volynski KE, Kullmann DM. Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 2395-2400. PMID: 28193892, PMCID: PMC5338558, DOI: 10.1073/pnas.1608763114.Peer-Reviewed Original ResearchConceptsSomatic depolarizationPotassium channelsAction potentialsPresynaptic potassium channelsPrimary hippocampal culturesSubthreshold membrane potential fluctuationsHeterozygous mouse modelEpisodic ataxia type 1Distinct potassium channelsSubthreshold modulationAxon transectionSmall boutonsCalcium influxHippocampal culturesMouse modelSynaptic boutonsKv1.1 subunitsMembrane potential fluctuationsNeurotransmitter releaseIntact axonsType 1Genetic deletionAtaxia type 1Further prolongationPresynaptic spikes