2018
S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi
Ernst AM, Syed SA, Zaki O, Bottanelli F, Zheng H, Hacke M, Xi Z, Rivera-Molina F, Graham M, Rebane AA, Björkholm P, Baddeley D, Toomre D, Pincet F, Rothman JE. S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi. Developmental Cell 2018, 47: 479-493.e7. PMID: 30458139, PMCID: PMC6251505, DOI: 10.1016/j.devcel.2018.10.024.Peer-Reviewed Original ResearchMeSH KeywordsBiological TransportCells, CulturedEndoplasmic ReticulumGolgi ApparatusHumansIntracellular MembranesLipoylationProtein TransportConceptsS-palmitoylationAnterograde cargoAnterograde signalMembrane cargoCargo selectionTransmembrane domainMembrane proteinsGolgi membranesGolgiSpecific signalsMembrane interfaceModel systemCargoProteinRate of transportAnterograde transportVesiclesCisternaeCurved regionsMembraneTransportRegionSignalsDomainFluorescenceThe Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling
Kofler N, Corti F, Rivera-Molina F, Deng Y, Toomre D, Simons M. The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling. Journal Of Biological Chemistry 2018, 293: 4805-4817. PMID: 29425100, PMCID: PMC5880142, DOI: 10.1074/jbc.m117.812172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndosomesEndothelial CellsMiceMice, Inbred BALB CProtein TransportProtein Tyrosine Phosphatase, Non-Receptor Type 1Rab GTP-Binding ProteinsRab4 GTP-Binding ProteinsRab7 GTP-Binding ProteinsSignal TransductionVascular Endothelial Growth Factor Receptor-2Vesicular Transport ProteinsConceptsEndosomal traffickingVascular endothelial growth factor receptor 2Phosphotyrosine phosphatase 1BVEGFR2 traffickingEndothelial growth factor receptor 2Small GTPase Rab4Rab effector proteinsEndothelial cell functionRab7-positive endosomesCell functionRab GTPaseSorting endosomesCell surface expressionMaster regulatorEndosomal compartmentsVEGFR2 degradationPhosphatase 1BRABEP2Dependent signalingVascular developmentVEGFR2 signalingHigh-resolution microscopyTraffickingEndosomesBiochemical assays
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 toolExocytosisOrganismsVesiclesDifferential 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
Optogenetic 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
2012
Caveolae, Fenestrae and Transendothelial Channels Retain PV1 on the Surface of Endothelial Cells
Tkachenko E, Tse D, Sideleva O, Deharvengt SJ, Luciano MR, Xu Y, McGarry CL, Chidlow J, Pilch PF, Sessa WC, Toomre DK, Stan RV. Caveolae, Fenestrae and Transendothelial Channels Retain PV1 on the Surface of Endothelial Cells. PLOS ONE 2012, 7: e32655. PMID: 22403691, PMCID: PMC3293851, DOI: 10.1371/journal.pone.0032655.Peer-Reviewed Original ResearchConceptsFormation of diaphragmsRemoval of caveolaeDynamin-independent pathwayAbsence of caveolaeEndothelial cellsProtein levelsCellular rolesCavin-1Knockout phenotypesPlasma membraneCaveolin-1CaveolaeLung endothelial cellsCell surfaceRapid internalizationInternalization rateAbundance of structuresMice resultsTransendothelial channelsEssential componentOnly roleFenestral diaphragmsCellsClathrinTranscription
2010
Spatial control of EGF receptor activation by reversible dimerization on living cells
Chung I, Akita R, Vandlen R, Toomre D, Schlessinger J, Mellman I. Spatial control of EGF receptor activation by reversible dimerization on living cells. Nature 2010, 464: 783-787. PMID: 20208517, DOI: 10.1038/nature08827.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell Line, TumorCell PolarityCell SurvivalCHO CellsCricetinaeCricetulusDiffusionEnzyme ActivationEnzyme StabilityEpidermal Growth FactorErbB ReceptorsGene Expression RegulationGRB2 Adaptor ProteinHumansKineticsLigandsProtein MultimerizationProtein TransportSignal TransductionThermodynamicsConceptsLigand bindingEpidermal growth factor receptor moleculeType I receptor kinaseEGF receptor activationDimer formationReceptor kinaseReceptor dimerizationDimerization dynamicsReceptor dimersLiving cellsReceptor moleculesCell marginsDimer populationSpatial controlHuman carcinomasConformation changeDimerizationCell centerReceptor activationRate of dissociationCellsBindingActivationKinaseReversible dimerization
2006
Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking
Iwakiri Y, Satoh A, Chatterjee S, Toomre DK, Chalouni CM, Fulton D, Groszmann RJ, Shah VH, Sessa WC. Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 19777-19782. PMID: 17170139, PMCID: PMC1750883, DOI: 10.1073/pnas.0605907103.Peer-Reviewed Original ResearchConceptsProtein S-nitrosylationS-nitrosylationN-ethylmaleimide-sensitive factorPlasma membrane caveolaeAlters protein functionSpecific cysteine residuesSpecific posttranslational modificationsSpecific S-nitrosylationS-nitrosylation reactionsIntracellular transport processesProtein traffickingMembrane caveolaeProtein functionProtein transportPosttranslational modificationsCysteine residuesPlasma membraneTarget proteinsENOS localizationGolgi apparatusEndoplasmic reticulumGolgiDiffusible natureNOS actionGenerate nitric oxideThe 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 glycoproteinPathwayLymphocyte 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
2004
Golgi duplication in Trypanosoma brucei
He CY, Ho HH, Malsam J, Chalouni C, West CM, Ullu E, Toomre D, Warren G. Golgi duplication in Trypanosoma brucei. Journal Of Cell Biology 2004, 165: 313-321. PMID: 15138289, PMCID: PMC2172185, DOI: 10.1083/jcb.200311076.Peer-Reviewed Original Research
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