2017
Long‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR
Thompson AD, Omar MH, Rivera‐Molina F, Xi Z, Koleske AJ, Toomre DK, Schepartz A. Long‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR. Angewandte Chemie International Edition 2017, 56: 10408-10412. PMID: 28679029, PMCID: PMC5576494, DOI: 10.1002/anie.201704783.Peer-Reviewed Original ResearchExcess 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
2016
Sphingomyelin is sorted at the trans Golgi network into a distinct class of secretory vesicle
Deng Y, Rivera-Molina FE, Toomre DK, Burd CG. Sphingomyelin is sorted at the trans Golgi network into a distinct class of secretory vesicle. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 6677-6682. PMID: 27247384, PMCID: PMC4914164, DOI: 10.1073/pnas.1602875113.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkSynthesis of sphingomyelinGolgi networkSecretory vesiclesPlasma membraneQuantitative live-cell imagingVesicular transport carriersSorting of proteinsGlycophosphatidylinositol-anchored proteinsPore-forming toxinsLive-cell imagingInterorganelle traffickingAbundant sphingolipidIntracellular traffickingSecretory proteinsSM transportTransport carriersProteinCell imagingTraffickingDistinct classesSpecific carrierVesiclesPrincipal functionSortingOptogenetic 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
2015
The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135
Stoops EH, Hull M, Olesen C, Mistry K, Harder JL, Rivera-Molina F, Toomre D, Caplan MJ. The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135. Journal Of Cell Biology 2015, 211: 287-294. PMID: 26504168, PMCID: PMC4621837, DOI: 10.1083/jcb.201502045.Peer-Reviewed Original ResearchConceptsPrimary ciliaSurface proteinsTrans-Golgi networkPolarized epithelial cellsApical surface proteinsSNAP-tag systemBasolateral plasma membraneCell surface proteinsEpithelial cellsApical proteinsPericiliary regionGolgi networkPolarized traffickingCarrier vesiclesProtein deliveryPlasma membraneApical membraneProteinGp135Basolateral membraneCiliaMembraneHot spotsCellsTrafficking
2013
Live-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
Optogenetic control of phosphoinositide metabolism
Idevall-Hagren O, Dickson EJ, Hille B, Toomre DK, De Camilli P. Optogenetic control of phosphoinositide metabolism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: e2316-e2323. PMID: 22847441, PMCID: PMC3435206, DOI: 10.1073/pnas.1211305109.Peer-Reviewed Original ResearchMeSH KeywordsActinsAmino Acid MotifsAnimalsArabidopsis ProteinsBinding SitesCell MembraneChlorocebus aethiopsCOS CellsCryptochromesEndocytosisHumansKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelLightMembrane PotentialsPC12 CellsPhosphatidylinositol 3-KinasesPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositolsPhosphoric Monoester HydrolasesPhosphorylationRatsRecombinant Fusion ProteinsSignal TransductionConceptsCryptochrome 2Membrane rufflingCellular functionsEndocytic clathrin-coated pitsMembrane-targeting motifClathrin-coated pitsLight-induced dimerizationMammalian cellsReversible dephosphorylationPlasma membraneDownstream effectorsPlant proteinsBlue light illuminationPI3KCellular assaysRegion domainsOptogenetic controlPhosphoinositideCell membraneCIBNPhosphoinositide metabolismDephosphorylationCompensatory accumulationRufflingLipid components
2011
Using light to see and control membrane traffic
Xu Y, Melia TJ, Toomre DK. Using light to see and control membrane traffic. Current Opinion In Chemical Biology 2011, 15: 822-830. PMID: 22079055, DOI: 10.1016/j.cbpa.2011.10.016.Peer-Reviewed Original ResearchSplice isoform estrogen receptors as integral transmembrane proteins
Kim KH, Toomre D, Bender JR. Splice isoform estrogen receptors as integral transmembrane proteins. Molecular Biology Of The Cell 2011, 22: 4415-4423. PMID: 21937726, PMCID: PMC3216666, DOI: 10.1091/mbc.e11-05-0416.Peer-Reviewed Original ResearchConceptsSplice isoformsTotal internal reflection fluorescence microscopySteroid hormone receptorsIntegral transmembrane proteinN-terminal ectodomainReflection fluorescence microscopyHormone receptorsTransmembrane proteinPlasma membraneProtein structureHuman endothelial cellsLigand engagementPotential novel therapeutic targetER46Fluorescence microscopyNovel therapeutic targetEcliptic pHluorinActivation signalsEndothelial nitric oxide synthase activationEstrogen receptor αENOS activationReceptor αIsoformsTherapeutic targetNitric oxide synthase activation
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 regionMidbodyMembraneFurrowRepair 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 system
2007
Par3 functions in the biogenesis of the primary cilium in polarized epithelial cells
Sfakianos J, Togawa A, Maday S, Hull M, Pypaert M, Cantley L, Toomre D, Mellman I. Par3 functions in the biogenesis of the primary cilium in polarized epithelial cells. Journal Of Cell Biology 2007, 179: 1133-1140. PMID: 18070914, PMCID: PMC2140027, DOI: 10.1083/jcb.200709111.Peer-Reviewed Original ResearchConceptsPrimary ciliaAtypical protein kinase CIntraflagellar transport particlesBasolateral membrane domainsMicrotubule-dependent transportProtein kinase CEpithelial cellsMembrane biogenesisPDZ proteinsMembrane domainsMembrane proteinsPar complexMicrotubule motorsCiliary membraneVectorial movementPar3 functionsKinesin-2Kinase CPar3Additional roleJunctional complexesCrumbs3Apical surfaceBiogenesisCiliaLoss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate
Zoncu R, Perera RM, Sebastian R, Nakatsu F, Chen H, Balla T, Ayala G, Toomre D, De Camilli PV. Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 3793-3798. PMID: 17360432, PMCID: PMC1805489, DOI: 10.1073/pnas.0611733104.Peer-Reviewed Original ResearchConceptsClathrin-coated pitsPlasma membraneRegulatory complexEndocytic clathrin-coated pitsClathrin coat dynamicsTotal internal reflection fluorescence microscopyFluorescent fusion proteinsActin regulatory proteinsEndocytic clathrin adaptorsReflection fluorescence microscopyEndocytic adaptorsClathrin spotsClathrin adaptorsActin regulationInducible recruitmentClathrin punctaAccessory factorsFusion proteinCell surfaceFluorescence microscopyP20 subunitAcute depletionDramatic lossAdaptorProtein
2006
The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor
Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nature Cell Biology 2006, 8: 971-977. PMID: 16906144, DOI: 10.1038/ncb1463.Peer-Reviewed Original ResearchConceptsGuanine nucleotide exchange factorsNucleotide exchange factorsType IV secretion apparatusIntracellular pathogen Legionella pneumophilaHost cellsEndoplasmic reticulum-derived vesiclesDot/IcmPathogen Legionella pneumophilaL. pneumophila mutantsRab1 recruitmentSubstrate proteinsRab familyExchange factorGTPase Rab1Secretion apparatusVesicular transportBacterial proteinsGolgi apparatusVisual screenEndoplasmic reticulumRab1Membrane transportSpecific membersDrrAIntracellular pathogensVectorial insertion of apical and basolateral membrane proteins in polarized epithelial cells revealed by quantitative 3D live cell imaging
Hua W, Sheff D, Toomre D, Mellman I. Vectorial insertion of apical and basolateral membrane proteins in polarized epithelial cells revealed by quantitative 3D live cell imaging. Journal Of Cell Biology 2006, 172: 1035-1044. PMID: 16567501, PMCID: PMC2063761, DOI: 10.1083/jcb.200512012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell LineCell MembraneCell PolarityDogsEndocytosisEpithelial CellsGlycoproteinsGlycosylphosphatidylinositolsGreen Fluorescent ProteinsKineticsLaser Scanning CytometryLuminescent ProteinsMembrane GlycoproteinsMembrane ProteinsNeural Cell Adhesion MoleculesProtein TransportRecombinant Fusion ProteinsTemperatureTransfectionTrans-Golgi NetworkTransport VesiclesViral Envelope ProteinsConceptsBasolateral membrane proteinsLive-cell imagingMembrane proteinsThree-dimensional live cell imagingGlycosylphosphatidylinositol-anchored proteinsVesicular stomatitis virus glycoproteinApical surfaceMadin-Darby canine kidney cellsCell imagingFilter-grown Madin-Darby canine kidney (MDCK) cellsEpithelial cellsBasolateral proteinsCanine kidney cellsTransport intermediatesVesicle dockingSecretory pathwayPlasma membraneVectorial insertionMembrane componentsJunctional complexesProteinRespective membranesKidney cellsVirus glycoproteinPathwaySpatio-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 sitesLymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains
Millán J, Hewlett L, Glyn M, Toomre D, Clark P, Ridley AJ. Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains. Nature Cell Biology 2006, 8: 113-123. PMID: 16429128, DOI: 10.1038/ncb1356.Peer-Reviewed Original ResearchMeSH KeywordsActinsAntibodies, MonoclonalCaveolaeCaveolin 1Cell AdhesionCell MembraneCell MovementCell Surface ExtensionsCells, CulturedEndothelial CellsE-SelectinHumansIntercellular Adhesion Molecule-1Lymphocyte ActivationLymphocytesMicroscopy, Electron, TransmissionMicroscopy, FluorescenceProtein TransportReceptor AggregationRNA, Small InterferingStress FibersT-LymphocytesTransfectionTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1
2005
Spying on IgE receptor signaling
Toomre D. Spying on IgE receptor signaling. Journal Of Cell Biology 2005, 171: 415-417. PMID: 16275748, PMCID: PMC2171246, DOI: 10.1083/jcb.200510105.Peer-Reviewed Original ResearchConceptsSignal transductionPlasma membrane organizationProtein-protein interactionsLipid raft microdomainsFluorescent correlation spectroscopyRaft microdomainsLipid raftsMembrane organizationIgE receptorTransductionPotential roleReceptorsCorrelation spectroscopyMicrodomainsRaftsCellsNew complexitiesComplexesDomain
2003
Nanometer targeting of microtubules to focal adhesions
Krylyshkina O, Anderson KI, Kaverina I, Upmann I, Manstein DJ, Small JV, Toomre DK. Nanometer targeting of microtubules to focal adhesions. Journal Of Cell Biology 2003, 161: 853-859. PMID: 12782685, PMCID: PMC2172972, DOI: 10.1083/jcb.200301102.Peer-Reviewed Original ResearchConceptsTotal internal reflection fluorescence microscopyAdhesion complexesIntact microtubule cytoskeletonReflection fluorescence microscopyGFP-CLIP-170Substrate adhesionFocal adhesionsMicrotubule cytoskeletonCell movementCell peripheryCommon cytoskeletal elementsMicrotubule tipsAdhesion fociCytoskeletal elementsPolymerizing microtubulesTip complexGFP-tubulinMicrotubule endsFluorescence microscopyMicrotubulesMultiple microtubulesSite targetingCentral roleComplexesTargeting
2002
Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane
Chow A, Toomre D, Garrett W, Mellman I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 2002, 418: 988-994. PMID: 12198549, DOI: 10.1038/nature01006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigens, CDCell DifferentiationCell MembraneCells, CulturedDendritic CellsEndocytosisEndosomesHistocompatibility Antigens Class IILysosome-Associated Membrane GlycoproteinsLysosomesMembrane GlycoproteinsMiceMice, Inbred C57BLMicroscopy, VideoProtein TransportStem CellsConceptsDendritic cellsMajor histocompatibility complex (MHC) class II moleculesLive dendritic cellsImmature dendritic cellsCo-stimulatory moleculesMHC II moleculesClass II moleculesInternalized antigensInflammatory mediatorsII-peptide complexesMHC-IIT lymphocytesImmune responseMHC class II transportPeptide antigensMaturation triggerClass II transportAntigenGreen fluorescent proteinCellsLysosomal compartmentPlasma membraneLysosomesTerminal degradative compartmentMicrobial products