2018
The 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
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 diabetes
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
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 components
2011
Splice 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
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 ResearchMeSH KeywordsAdipocytesAnimalsExocytosisInsulinMarkov ChainsMicroscopy, FluorescenceProbabilitySecretory VesiclesSignal TransductionConceptsTotal 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 snapshotsSpatial 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
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 ResearchMeSH KeywordsAnimalsChlorocebus aethiopsClathrin-Coated VesiclesCOS CellsEndocytosisEndosomesPhosphatidylinositolsSignal TransductionConceptsPositive 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
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 ResearchMeSH KeywordsCell LineCell MembraneComputer SimulationEpithelial CellsExocytosisMembrane FusionMembrane ProteinsModels, BiologicalSignal TransductionConceptsEvanescent 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
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