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
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
2007
A 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