2017
Excess cholesterol inhibits glucose‐stimulated fusion pore dynamics in insulin exocytosis
Xu Y, Toomre DK, Bogan JS, Hao M. Excess cholesterol inhibits glucose‐stimulated fusion pore dynamics in insulin exocytosis. Journal Of Cellular And Molecular Medicine 2017, 21: 2950-2962. PMID: 28544529, PMCID: PMC5661106, DOI: 10.1111/jcmm.13207.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell MembraneCholesterolDiabetes Mellitus, Type 2DynaminsExocytosisGene Expression RegulationGlucoseHumansInsulinInsulin-Secreting CellsMembrane FusionMiceMicroscopy, FluorescenceModels, BiologicalPhosphatidylinositol 4,5-DiphosphateSecretory VesiclesSignal TransductionConceptsFusion pore dynamicsInsulin exocytosisFusion eventsPore dynamicsGlucose-triggered insulin secretionΒ-cellsFull fusionSingle granule levelTotal internal reflection fluorescence microscopySingle exocytic eventsReflection fluorescence microscopyImpairs β-cell functionExcess cholesterolGTPase dynaminExocytic eventsRole of cholesterolPlasma membranePancreatic β-cellsMolecular mechanismsInsulin granulesCompound exocytosisFusion kineticsΒ-cell dysfunctionExocytosisType 2 diabetesDifferential requirement for N‐ethylmaleimide‐sensitive factor in endosomal trafficking of transferrin receptor from anterograde trafficking of vesicular stomatitis virus glycoprotein G
Fan J, Zhou X, Wang Y, Kuang C, Sun Y, Liu X, Toomre D, Xu Y. Differential requirement for N‐ethylmaleimide‐sensitive factor in endosomal trafficking of transferrin receptor from anterograde trafficking of vesicular stomatitis virus glycoprotein G. FEBS Letters 2017, 591: 273-281. PMID: 27995606, DOI: 10.1002/1873-3468.12532.Peer-Reviewed Original ResearchConceptsVesicular stomatitis virus glycoprotein GGolgi structureDifferential requirementN-ethylmaleimide-sensitive factorConstitutive trafficking pathwayTrafficking pathwaysGlycoprotein GTransferrin endocytosisEndosomal traffickingAnterograde traffickingGolgi fragmentationMammalian cellsVesicular transportDifferent vesiclesHeLa cellsReceptor exocytosisTraffickingTransferrin receptorFusion factorKnockdownCell viabilityCentral rolePathwayCrucial roleCells
2016
Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation
Zhou HJ, Qin L, Zhang H, Tang W, Ji W, He Y, Liang X, Wang Z, Yuan Q, Vortmeyer A, Toomre D, Fuh G, Yan M, Kluger MS, Wu D, Min W. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nature Medicine 2016, 22: 1033-1042. PMID: 27548575, PMCID: PMC5014607, DOI: 10.1038/nm.4169.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1Angiopoietin-2AnimalsApoptosis Regulatory ProteinsBrainEndothelium, VascularEnzyme-Linked Immunosorbent AssayExocytosisFluorescent Antibody TechniqueGene Expression ProfilingHemangioma, Cavernous, Central Nervous SystemHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNerve Tissue ProteinsProto-Oncogene ProteinsReceptor, TIE-2Vesicle-Associated Membrane Protein 3Optogenetic activation reveals distinct roles of PIP3 and Akt in adipocyte insulin action
Xu Y, Nan D, Fan J, Bogan JS, Toomre D. Optogenetic activation reveals distinct roles of PIP3 and Akt in adipocyte insulin action. Journal Of Cell Science 2016, 129: 2085-2095. PMID: 27076519, PMCID: PMC4878990, DOI: 10.1242/jcs.174805.Peer-Reviewed Original ResearchConceptsPI3KGLUT4 translocationDistinct rolesAkt-independent pathwayNew optogenetic toolsGlucose transporter 4Drug-mediated inhibitionTranslocation responseIntracellular vesiclesOverall insulin actionPlasma membraneInsulin actionN-terminusOptogenetic toolsInsulin stimulationTransporter 4Biochemical assaysAktTranslocationAdipose cellsVesiclesPathwayCIB1PIP3Cells
2013
A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils
Zhang Y, Tang W, Zhang H, Niu X, Xu Y, Zhang J, Gao K, Pan W, Boggon TJ, Toomre D, Min W, Wu D. A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils. Developmental Cell 2013, 27: 215-226. PMID: 24176643, PMCID: PMC3834565, DOI: 10.1016/j.devcel.2013.09.021.Peer-Reviewed Original ResearchConceptsNeutrophil degranulationAcute innate immune responseIschemia-reperfusion injuryInnate immune responseProtection of kidneyNeutrophil functionImmune responseInhibition of exocytosisTissue damageGranule poolGranule contentsDegranulationImportant regulatorImportant roleVesicle exocytosisExocytosisSTK24InjuryNeutrophilsKidneyUNC13DLive-cell imaging of exocyst links its spatiotemporal dynamics to various stages of vesicle fusion
Rivera-Molina F, Toomre D. Live-cell imaging of exocyst links its spatiotemporal dynamics to various stages of vesicle fusion. Journal Of Cell Biology 2013, 201: 673-680. PMID: 23690179, PMCID: PMC3664709, DOI: 10.1083/jcb.201212103.Peer-Reviewed Original ResearchConceptsLive-cell imagingVesicle fusionEndocytic recycling compartmentAttachment protein receptorsSNARE fusion machineryExocyst complexMembrane traffickingFusion machineryRecycling compartmentCell cortexSec8Cell protrusionsPlasma membraneVesicle attachmentFusion poreMembrane expansionProtein receptorsCell polarizationFluorescence recoverySpatiotemporal dynamicsExocystUbiquitous roleVesiclesTraffickingMorphological criteria
2012
Generating live cell data using total internal reflection fluorescence microscopy.
Toomre D. Generating live cell data using total internal reflection fluorescence microscopy. Cold Spring Harbor Protocols 2012, 2012: 439-46. PMID: 22474670, DOI: 10.1101/pdb.ip068676.Peer-Reviewed Original ResearchConceptsTotal internal reflection fluorescence microscopyReflection fluorescence microscopyThinner optical planeDynamic cellular processesFluorescence microscopyLive-cell dataCell fluorescent microscopyRefractive indexHigh numerical aperture objective lensNumerical aperture objective lensMembrane traffickingCytoskeleton dynamicsCellular processesCytoskeleton remodelingCell cortexCell signalingTime-lapse moviesDifferent refractive indicesOrganelle levelTransient intermediate statesMolecular manipulationConventional epifluorescence microscopeDeep imagingEvanescent fieldObjective lens
2011
Dual-mode of insulin action controls GLUT4 vesicle exocytosis
Xu Y, Rubin BR, Orme CM, Karpikov A, Yu C, Bogan JS, Toomre DK. Dual-mode of insulin action controls GLUT4 vesicle exocytosis. Journal Of Cell Biology 2011, 193: 643-653. PMID: 21555461, PMCID: PMC3166865, DOI: 10.1083/jcb.201008135.Peer-Reviewed Original ResearchMeSH Keywords3T3-L1 CellsAdipocytesAnimalsBiosensing TechniquesCarrier ProteinsExocytosisGlucose Transporter Type 4Green Fluorescent ProteinsInsulinIntracellular Signaling Peptides and ProteinsKineticsMembrane FusionMiceMicroscopy, FluorescenceMicroscopy, VideoPhospholipase DRecombinant Fusion ProteinsRNA InterferenceTransfectionTransport VesiclesVesicle-Associated Membrane Protein 2ConceptsGLUT4 storage vesiclesVesicle exocytosisInsulin-stimulated control cellsGLUT4 vesicle exocytosisPlasma membrane fusionNovel regulatory siteSingle vesicle exocytosisInsulin triggersVesicle trafficExocytic rateFusion poreSurface of adipocytesMembrane fusionRegulatory sitesPhospholipase DStorage vesiclesPore expansionExocytosisControl cellsAcute perturbationVesiclesInsulin actionVesicle characteristicsAdipocytesCellsExocyst function regulated by effector phosphorylation
Chen XW, Leto D, Xiao J, Goss J, Wang Q, Shavit JA, Xiong T, Yu G, Ginsburg D, Toomre D, Xu Z, Saltiel AR. Exocyst function regulated by effector phosphorylation. Nature Cell Biology 2011, 13: 580-588. PMID: 21516108, PMCID: PMC3904505, DOI: 10.1038/ncb2226.Peer-Reviewed Original ResearchConceptsInsulin-stimulated GLUT4 exocytosisProtein kinase CGLUT4 vesiclesExocyst functionGLUT4 exocytosisUndergoes phosphorylationExocytic vesiclesPhosphorylation eventsContinuous exocytosisSmall GTPasesPhosphorylation sitesZebrafish embryosTrafficking processesBinding domainsSite of fusionEffector phosphorylationExocystBearing mutationsKinase CG proteinsPhosphorylationVesiclesRalAEpithelial cellsExocytosis
2010
Deciphering subcellular processes in live imaging datasets via dynamic probabilistic networks
Letinic K, Sebastian R, Barthel A, Toomre D. Deciphering subcellular processes in live imaging datasets via dynamic probabilistic networks. Bioinformatics 2010, 26: 2029-2036. PMID: 20581401, PMCID: PMC2916721, DOI: 10.1093/bioinformatics/btq331.Peer-Reviewed Original ResearchConceptsTotal internal reflection fluorescence microscopyCellular statesDistinct cellular statesSpatial-temporal regulationNon-polarized cellsComplex intracellular processesReflection fluorescence microscopyLive cell imaging dataOrganelle behaviorGLUT4 vesiclesProtein complexesCellular processesSpatial regulationDevelopmental processesBiological processesSubcellular processesCell imaging dataCell polarizationLiving cellsIntracellular processesBlood glucose homeostasisFluorescence microscopyExocytosisCell imagingStatic snapshots
2008
Both daughter cells traffic and exocytose membrane at the cleavage furrow during mammalian cytokinesis
Goss JW, Toomre DK. Both daughter cells traffic and exocytose membrane at the cleavage furrow during mammalian cytokinesis. Journal Of Cell Biology 2008, 181: 1047-1054. PMID: 18573914, PMCID: PMC2442215, DOI: 10.1083/jcb.200712137.Peer-Reviewed Original ResearchConceptsDaughter cellsTotal internal reflection fluorescence microscopy imagingCleavage furrowAdvanced live-cell imaging techniquesConfocal time-lapse imagingLive-cell imaging techniquesCell imaging techniquesReserve vesicle poolTime-lapse imagingMidbody abscissionMammalian cytokinesisFluorescence microscopy imagingFluorescent proteinPhotobleaching experimentsCytokinesisVesicle poolLysosomal compartmentIndividual vesiclesSingle vesiclesVesiclesGolgiFurrow regionMidbodyMembraneFurrow
2006
Spatio-Temporal Analysis of Constitutive Exocytosis in Epithelial Cells
Sebastian R, Diaz ME, Ayala G, Letinic K, Moncho-Bogani J, Toomre D. Spatio-Temporal Analysis of Constitutive Exocytosis in Epithelial Cells. IEEE/ACM Transactions On Computational Biology And Bioinformatics 2006, 3: 17-32. PMID: 17048390, DOI: 10.1109/tcbb.2006.11.Peer-Reviewed Original ResearchConceptsEvanescent wave microscopyPlethora of moleculesProtein targetingConstitutive exocytosisVesicular trafficFusion eventsPlasma membraneVesicle fusionBiological hypothesesExocytosisRipley's K-functionWave microscopyFusion siteEpithelial cellsStudy of membranesPathological conditionsK-functionFinal stepMembraneProper distributionTransportersFusionEnzymeSitesSpatial sites
2005
Phosphatidylinositol phosphate kinase type Iγ regulates dynamics of large dense-core vesicle fusion
Gong LW, Di Paolo G, Diaz E, Cestra G, Diaz ME, Lindau M, De Camilli P, Toomre D. Phosphatidylinositol phosphate kinase type Iγ regulates dynamics of large dense-core vesicle fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 5204-5209. PMID: 15793002, PMCID: PMC555604, DOI: 10.1073/pnas.0501412102.Peer-Reviewed Original ResearchConceptsDense-core vesicle fusionLarge dense-core vesicle fusionLarge dense-core vesicle (LDCV) exocytosisDense-core vesicle exocytosisFusion pore expansionDirect genetic evidenceReleasable vesicle poolType IγVesicle exocytosisGenetic evidenceVesicle primingBisphosphate synthesisVesicle fusionKinetics of secretionImportant regulatorVesicle poolPore expansionNeuroendocrine tissuesPhosphatidylinositolFusion dynamicsChromaffin cellsI gammaKey role