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
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
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 cells