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
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 ResearchAutomatic Detection of Large Dense-Core Vesicles in Secretory Cells and Statistical Analysis of Their Intracellular Distribution
Díaz E, Ayala G, Díaz ME, Gong LW, Toomre D. Automatic Detection of Large Dense-Core Vesicles in Secretory Cells and Statistical Analysis of Their Intracellular Distribution. IEEE/ACM Transactions On Computational Biology And Bioinformatics 2008, 7: 2-11. PMID: 20150664, DOI: 10.1109/tcbb.2008.30.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAnimalsAnimals, NewbornArtificial IntelligenceCells, CulturedChromaffin CellsChromaffin GranulesComputer SimulationData Interpretation, StatisticalImage EnhancementImage Interpretation, Computer-AssistedInformation Storage and RetrievalMiceMicroscopy, ElectronModels, BiologicalModels, StatisticalPattern Recognition, AutomatedReproducibility of ResultsSecretory VesiclesSensitivity and SpecificityConceptsPlasma membraneLarge dense-core vesiclesDense-core vesiclesDifferent spatial point processesRegulated exocytosisLocation of granulesStudy of secretionIntracellular distributionCell cytoplasmSecretory cellsDysfunctional secretionDifferent cellsFunctional descriptorsDifferent cell groupsAnalysis of diseasesVesiclesCellsMembraneNovel toolCell groupsDensity of granulesGranulesExocytosisCytoplasmMorphological appearance
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 surfaceBiogenesisCiliaA 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
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