2017
Novel ecto-tagged integrins reveal their trafficking in live cells
Huet-Calderwood C, Rivera-Molina F, Iwamoto DV, Kromann EB, Toomre D, Calderwood DA. Novel ecto-tagged integrins reveal their trafficking in live cells. Nature Communications 2017, 8: 570. PMID: 28924207, PMCID: PMC5603536, DOI: 10.1038/s41467-017-00646-w.Peer-Reviewed Original ResearchConceptsIntegrin functionΒ1 integrinLive cellsCell surface adhesion receptorsHeterodimeric cell-surface adhesion receptorsIntegrin endocytosisMulticellular organismsNovel powerful toolFocal adhesionsKnockout fibroblastsIntegrin activationAdhesion receptorsExtracellular loopIntegrinsTraffickingMajor mysteriesCellsTagsAdhesionHaloTagEndocytosisPowerful toolExocytosisOrganismsVesiclesExcess 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 diabetes
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 exocytosisExocytosisSTK24InjuryNeutrophilsKidneyUNC13D
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
2009
Exocyst is involved in polarized cell migration and cerebral cortical development
Letinic K, Sebastian R, Toomre D, Rakic P. Exocyst is involved in polarized cell migration and cerebral cortical development. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 11342-11347. PMID: 19549839, PMCID: PMC2708724, DOI: 10.1073/pnas.0904244106.Peer-Reviewed Original ResearchConceptsCell migrationDelivery of vesiclesNeuronal migrationVesicle tetheringExocyst complexMembrane trafficExocytic pathwayProtein complexesExocytic processExocystSpatial regulationEmbryonic developmentVesicle exocytosisSecretory vesiclesPlasma membraneTIRF microscopyPostmitotic cellsCortical neuronal migrationProper developmentCerebral cortical developmentWound assaysExocytosisVesiclesMembraneCells
2008
Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis
Idone V, Tam C, Goss JW, Toomre D, Pypaert M, Andrews NW. Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. Journal Of Cell Biology 2008, 180: 905-914. PMID: 18316410, PMCID: PMC2265401, DOI: 10.1083/jcb.200708010.Peer-Reviewed Original ResearchConceptsPlasma membraneStreptolysin OPore-forming proteinsPlasma membrane lesionsBacterial toxin streptolysin OEnhancement of endocytosisDependent endocytosisToxin streptolysin OImportant new insightsMembrane resealingLysosomal organellesEndocytosisMicrobial toxinsNovel pathwayExocytosisRepair processMembrane lesionsProteinNew insightsMembraneRapid Ca2ResealingRapid repair processCellsImmune systemAutomatic Detection of Large Dense-Core Vesicles in Secretory Cells and Statistical Analysis of Their Intracellular Distribution
Díaz E, Ayala G, Díaz ME, Gong LW, Toomre D. Automatic Detection of Large Dense-Core Vesicles in Secretory Cells and Statistical Analysis of Their Intracellular Distribution. IEEE/ACM Transactions On Computational Biology And Bioinformatics 2008, 7: 2-11. PMID: 20150664, DOI: 10.1109/tcbb.2008.30.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAnimalsAnimals, NewbornArtificial IntelligenceCells, CulturedChromaffin CellsChromaffin GranulesComputer SimulationData Interpretation, StatisticalImage EnhancementImage Interpretation, Computer-AssistedInformation Storage and RetrievalMiceMicroscopy, ElectronModels, BiologicalModels, StatisticalPattern Recognition, AutomatedReproducibility of ResultsSecretory VesiclesSensitivity and SpecificityConceptsPlasma membraneLarge dense-core vesiclesDense-core vesiclesDifferent spatial point processesRegulated exocytosisLocation of granulesStudy of secretionIntracellular distributionCell cytoplasmSecretory cellsDysfunctional secretionDifferent cellsFunctional descriptorsDifferent cell groupsAnalysis of diseasesVesiclesCellsMembraneNovel toolCell groupsDensity of granulesGranulesExocytosisCytoplasmMorphological appearance
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