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
Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells
Rauch L, Hennings K, Trasak C, Röder A, Schröder B, Koch-Nolte F, Rivera-Molina F, Toomre D, Aepfelbacher M. Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells. Journal Of Cell Science 2016, 129: 2937-2949. PMID: 27311480, PMCID: PMC5004874, DOI: 10.1242/jcs.186213.Peer-Reviewed Original ResearchConceptsEndocytic vesiclesActin polymerizationEndothelial cell invasionExocyst complexPhagocytic cupsPhagocytic cup-like structuresCell invasionPhagocytic cup closureArp2/3 complexN-WASPCup closureCup-like structuresCdc42GAPCdc42Human endothelial cellsCell functionVesiclesAnalogous mechanismInvasionEndothelial cellsExocystComplexesEndosomes
2013
The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis
Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, Prahst C, Zhang J, Wang Y, Davis G, Toomre D, Ruhrberg C, Simons M. The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis. Developmental Cell 2013, 25: 156-168. PMID: 23639442, PMCID: PMC3774154, DOI: 10.1016/j.devcel.2013.03.019.Peer-Reviewed Original ResearchAnimalsArteriesCells, CulturedCytoplasmEndocytosisEndosomesEndothelium, VascularMAP Kinase Signaling SystemMiceMorphogenesisNeovascularization, PathologicNeuropilin-1PhosphorylationSignal TransductionTransferrinVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Vesicular Transport Proteins
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 componentsGenerating 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
2010
The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics
Nakatsu F, Perera RM, Lucast L, Zoncu R, Domin J, Gertler FB, Toomre D, De Camilli P. The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics. Journal Of Cell Biology 2010, 190: 307-315. PMID: 20679431, PMCID: PMC2922640, DOI: 10.1083/jcb.201005018.Peer-Reviewed Original ResearchConceptsClathrin-coated pitsNegative regulatorEndocytic clathrin-coated pitsClathrin-coated pit dynamicsPit maturationCCP lifetimeProduct phosphatidylinositolCoat assemblyCellular functionsMajor phosphoinositidePlasma membraneSHIP2SHIP2 expressionPit dynamicsDependent signalingReceptor signalingPhosphatidylinositolPhosphoinositide metabolismSignalingRegulatorInositolIntersectinPositive roleClathrinEndocytosis
2009
A Phosphoinositide Switch Controls the Maturation and Signaling Properties of APPL Endosomes
Zoncu R, Perera RM, Balkin DM, Pirruccello M, Toomre D, De Camilli P. A Phosphoinositide Switch Controls the Maturation and Signaling Properties of APPL Endosomes. Cell 2009, 136: 1110-1121. PMID: 19303853, PMCID: PMC2705806, DOI: 10.1016/j.cell.2009.01.032.Peer-Reviewed Original ResearchConceptsPositive endosomesAPPL endosomesEndocytic pathwayGrowth factor receptor traffickingEarly endocytic pathwayRab5-positive endosomesSingle-vesicle imagingGrowth factor signalingNovel endocytic compartmentsSurprising plasticityEndocytic vesiclesFactor signalingEndocytic compartmentsEnhanced growth factor signalingReceptor traffickingEndosomesSignaling propertiesRecent identificationPI3PCritical roleCurrent understandingSignalingPathwayFunctional organizationMaturation
2008
Analyzing Protein-Protein Spatial-Temporal Dependencies from Image Sequences Using Fuzzy Temporal Random Sets
Daz M, Ayala G, Len T, Zoncu R, Toomre D. Analyzing Protein-Protein Spatial-Temporal Dependencies from Image Sequences Using Fuzzy Temporal Random Sets. Journal Of Computational Biology 2008, 15: 1221-1236. PMID: 18973437, DOI: 10.1089/cmb.2008.0055.Peer-Reviewed Original ResearchConceptsTotal internal reflection fluorescence microscopyFluorescent-tagged proteinsReflection fluorescence microscopyEndocytic proteinsBiological questionsPlasma membraneDifferent proteinsFluorescence microscopyProteinSequenceK-functionArea of fluorescenceEndocytosisFree tuning parametersGFPBiologistsColocalizationHigh spatial-temporal resolutionMembraneSpatial-temporal resolutionPoisson cluster modelCellsFluorescenceMeasuring Spatiotemporal Dependencies in Bivariate Temporal Random Sets with Applications to Cell Biology
Diaz E, Sebastian R, Ayala G, Diaz M, Zoncu R, Toomre D, Gasman S. Measuring Spatiotemporal Dependencies in Bivariate Temporal Random Sets with Applications to Cell Biology. IEEE Transactions On Pattern Analysis And Machine Intelligence 2008, 30: 1659-1671. PMID: 18617722, DOI: 10.1109/tpami.2007.70821.Peer-Reviewed Original ResearchRepair 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
Internalization, Intracellular Trafficking, Biodistribution of Monoclonal Antibody 806: A Novel Anti-Epidermal Growth Factor Receptor Antibody
Perera RM, Zoncu R, Johns TG, Pypaert M, Lee FT, Mellman I, Old LJ, Toomre DK, Scott AM. Internalization, Intracellular Trafficking, Biodistribution of Monoclonal Antibody 806: A Novel Anti-Epidermal Growth Factor Receptor Antibody. Neoplasia 2007, 9: 1099-1110. PMID: 18084617, PMCID: PMC2134906, DOI: 10.1593/neo.07721.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorMonoclonal antibody 806EGFR antibodyAnti-epidermal growth factor receptor (EGFR) antibodiesGrowth factor receptor antibodyHuman tumor xenograftsSynergistic antitumor activityNude mouse modelXenografted nude mouse modelSignificant therapeutic efficacyGrowth factor receptorPoor prognosisReceptor antibodiesEGFR therapeuticsEpithelial tumorsMouse modelTumor xenograftsNude miceSingle agentToxin conjugatesTherapeutic efficacyTherapeutic useTumor modelBiodistribution analysisTumor cellsA Role of the Lowe Syndrome Protein OCRL in Early Steps of the Endocytic Pathway
Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P. A Role of the Lowe Syndrome Protein OCRL in Early Steps of the Endocytic Pathway. Developmental Cell 2007, 13: 377-390. PMID: 17765681, PMCID: PMC2025683, DOI: 10.1016/j.devcel.2007.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCarrier ProteinsCell LineChlorocebus aethiopsClathrin-Coated VesiclesCOS CellsCrystallography, X-RayEndocytosisEndosomesGlutathione TransferaseGreen Fluorescent ProteinsHumansKidneyModels, BiologicalModels, MolecularMolecular Sequence DataMutationPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositolsPhosphoric Monoester HydrolasesPhosphorylationProtein Structure, SecondaryProtein Structure, TertiaryRecombinant Fusion ProteinsSequence Homology, Amino AcidTime FactorsConceptsEndocytic pathwayLike domainEndocytic clathrin-coated pitsLowe syndrome protein OCRLRole of OCRLEarly endocytic pathwayClathrin-coated pitsPeripheral early endosomesPhosphatase domainMembrane traffickingEarly endosomesGrowth factor receptorProtein networkClathrin boxOCRLDisease mutationsCell surfaceEarly stepsLowe syndromeFactor receptorRenal Fanconi syndromeDisease mechanismsMembrane interfaceAPPL1Predominant localizationLoss 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
Vectorial 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 ProteinsTemperatureTrans-Golgi NetworkTransfectionTransport 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 glycoproteinPathwayAnalysis of spatial dependencies of endocytic proteins based on temporal random sets
Sebastian R, Diaz M, Ayala G, Zoncu R, Toomre D. Analysis of spatial dependencies of endocytic proteins based on temporal random sets. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2006, 2006: 4175-4178. PMID: 17946228, DOI: 10.1109/iembs.2006.260479.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