2024
Unraveling cellular complexity with transient adapters in highly multiplexed super-resolution imaging
Schueder F, Rivera-Molina F, Su M, Marin Z, Kidd P, Rothman J, Toomre D, Bewersdorf J. Unraveling cellular complexity with transient adapters in highly multiplexed super-resolution imaging. Cell 2024, 187: 1769-1784.e18. PMID: 38552613, DOI: 10.1016/j.cell.2024.02.033.Peer-Reviewed Original ResearchConceptsInter-organelle contactsSuper-resolutionMultiplexed super-resolution microscopyIntricate spatial relationshipsGolgi stacksMammalian cellsCellular functionsSuper-resolution microscopyPrimary ciliaSuper-resolution fluorescence microscopyCellular complexityTransient adaptationFluorescence microscopyDNA-PAINTFluorogenic labelingMolecular targetsSpatial relationshipsImagesThroughputMechanisms of vesicle docking and fusion pore expansion by calcium-sensor synaptotagmin-1
Cheppali S, Tsemperouli M, Chetrit D, Rivera-Molina F, Toomre D, Karatekin E. Mechanisms of vesicle docking and fusion pore expansion by calcium-sensor synaptotagmin-1. Biophysical Journal 2024, 123: 381a. DOI: 10.1016/j.bpj.2023.11.2328.Peer-Reviewed Original Research
2023
Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies
Kume K, Lee J, Cheng Z, Robinson M, Leveille E, Cosgun K, Chan L, Feng Y, Arce D, Khanduja D, Toomre D, Müschen M. Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies. Blood 2023, 142: 4138. DOI: 10.1182/blood-2023-190926.Peer-Reviewed Original ResearchB-cell malignanciesB-cell lymphomaMature B-cell lymphomasB cell deathB cellsB cell developmentGenetic deletionMantle cell lymphomaNF-kB signalingBCR signal inhibitorsB cell precursorsCell of originCell viabilityChronic active BCRB cell survivalB cell receptor signalsHodgkin's diseaseMultiple myelomaNormal B cell developmentPlasma cellsBtk tyrosine kinaseCell lymphomaBurkitt's lymphomaNF-kBSmall molecule inhibitors
2019
New software for automated cilia detection in cells (ACDC)
Lauring MC, Zhu T, Luo W, Wu W, Yu F, Toomre D. New software for automated cilia detection in cells (ACDC). Cilia 2019, 8: 1. PMID: 31388414, PMCID: PMC6670212, DOI: 10.1186/s13630-019-0061-z.Peer-Reviewed Original ResearchManual analysisNew softwareData setsHighest F1 scoreTraditional manual analysisSoftware applicationsF1 scoreDetection accuracyUser biasRepresentative imagesInput dataSoftwareIntensity standard deviationEntire data setMain stepsParameter combinationsFalse positivesExperimental data setsKey metricsImagesSpeed enhancementAccuracyFalse negative rateMicroscopic imagesImage magnificationAcylation – A New Means to Control Traffic Through the Golgi
Ernst AM, Toomre D, Bogan JS. Acylation – A New Means to Control Traffic Through the Golgi. Frontiers In Cell And Developmental Biology 2019, 7: 109. PMID: 31245373, PMCID: PMC6582194, DOI: 10.3389/fcell.2019.00109.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsDiverse protein clientsSorting of proteinsIntegral membrane proteinsProtein clientsS-acylationGolgi networkProtein adaptersMembrane proteinsAnterograde fluxLipid modificationGolgi cisternaeGolgiLipid acylationNeurodegenerative diseasesHuman physiologyProteinPotential relevanceOrganellesRecent dataRapid trafficAcylationCisternaePhysiologyCargoMechanismLabeling Strategies Matter for Super-Resolution Microscopy: A Comparison between HaloTags and SNAP-tags
Erdmann RS, Baguley SW, Richens JH, Wissner RF, Xi Z, Allgeyer ES, Zhong S, Thompson AD, Lowe N, Butler R, Bewersdorf J, Rothman JE, St Johnston D, Schepartz A, Toomre D. Labeling Strategies Matter for Super-Resolution Microscopy: A Comparison between HaloTags and SNAP-tags. Cell Chemical Biology 2019, 26: 584-592.e6. PMID: 30745239, PMCID: PMC6474801, DOI: 10.1016/j.chembiol.2019.01.003.Peer-Reviewed Original Research
2018
Seeing the long tail: A novel green fluorescent protein, SiriusGFP, for ultra long timelapse imaging
Zhong S, Rivera-Molina F, Rivetta A, Toomre D, Santos-Sacchi J, Navaratnam D. Seeing the long tail: A novel green fluorescent protein, SiriusGFP, for ultra long timelapse imaging. Journal Of Neuroscience Methods 2018, 313: 68-76. PMID: 30578868, PMCID: PMC9431725, DOI: 10.1016/j.jneumeth.2018.12.008.Peer-Reviewed Original ResearchConceptsSuper-resolution structured illumination microscopyFluorescent proteinNovel green fluorescent proteinGreen fluorescent proteinMembrane proteinsPhotostable variantsCell biologyC-terminusStructured illumination microscopyEGFPProteinConfocal imagingSIM imagingCombination of novelIllumination microscopyKey mutationsKnown mutationsOmp25High intensity excitationMutationsLight intensityCo-operative effectSustained fluorescencePhotobleachingMisfoldingS-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi
Ernst AM, Syed SA, Zaki O, Bottanelli F, Zheng H, Hacke M, Xi Z, Rivera-Molina F, Graham M, Rebane AA, Björkholm P, Baddeley D, Toomre D, Pincet F, Rothman JE. S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi. Developmental Cell 2018, 47: 479-493.e7. PMID: 30458139, PMCID: PMC6251505, DOI: 10.1016/j.devcel.2018.10.024.Peer-Reviewed Original ResearchConceptsS-palmitoylationAnterograde cargoAnterograde signalMembrane cargoCargo selectionTransmembrane domainMembrane proteinsGolgi membranesGolgiSpecific signalsMembrane interfaceModel systemCargoProteinRate of transportAnterograde transportVesiclesCisternaeCurved regionsMembraneTransportRegionSignalsDomainFluorescenceAssessing photodamage in live-cell STED microscopy
Kilian N, Goryaynov A, Lessard MD, Hooker G, Toomre D, Rothman JE, Bewersdorf J. Assessing photodamage in live-cell STED microscopy. Nature Methods 2018, 15: 755-756. PMID: 30275592, PMCID: PMC6915835, DOI: 10.1038/s41592-018-0145-5.Peer-Reviewed Original ResearchThe 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
Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion
Hoang D, Broer N, Sosa JA, Abitbol N, Yao X, Li F, Rivera-Molina F, Toomre DK, Roman SA, Sue G, Kim S, Li AY, Callender GG, Simpson C, Narayan D. Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion. Annals Of Surgery 2017, 266: 1075-1083. PMID: 27611607, DOI: 10.1097/sla.0000000000002004.Peer-Reviewed Original ResearchConceptsParathyroid hormone secretionParathyroid glandsHormone secretionLeptin receptorOb/ob miceDiseased parathyroid glandsDiseased parathyroid tissueDiagnosis of hyperparathyroidismParathyroid chief cellsCultured parathyroid cellsAnimal model assaysJAK2/STAT3 inhibitorPTH levelsPTH secretionPTH releaseSerum calciumSitu hybridizationLeptin uptakeProspective studySurgical interventionConfocal microscopyHyperplastic glandsParathyroid tissueBone metabolismOb miceSTED Imaging of Golgi Dynamics with Cer-SiR: A Two-Component, Photostable, High-Density Lipid Probe for Live Cells
Erdmann RS, Toomre D, Schepartz A. STED Imaging of Golgi Dynamics with Cer-SiR: A Two-Component, Photostable, High-Density Lipid Probe for Live Cells. Methods In Molecular Biology 2017, 1663: 65-78. PMID: 28924659, PMCID: PMC6146391, DOI: 10.1007/978-1-4939-7265-4_6.Peer-Reviewed Original ResearchConceptsLive cellsMembrane-bound proteinsLipid probesGolgi dynamicsCellular functionsGolgi structureCellular organellesGolgi apparatusCeramide lipidsSuper-resolution imagingLabeling strategySTED imagingSTED microscopyCellsPhotostable fluorophoresLipidsGolgiOrganellesTwo-componentBioorthogonal reactionsProbeProteinHigh densityNovel 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 toolExocytosisOrganismsVesiclesLand-locked mammalian Golgi reveals cargo transport between stable cisternae
Dunlop MH, Ernst AM, Schroeder LK, Toomre DK, Lavieu G, Rothman JE. Land-locked mammalian Golgi reveals cargo transport between stable cisternae. Nature Communications 2017, 8: 432. PMID: 28874656, PMCID: PMC5585379, DOI: 10.1038/s41467-017-00570-z.Peer-Reviewed Original ResearchHIDE Probes: A New Toolkit for Visualizing Organelle Dynamics, Longer and at Super-Resolution
Thompson AD, Bewersdorf J, Toomre D, Schepartz A. HIDE Probes: A New Toolkit for Visualizing Organelle Dynamics, Longer and at Super-Resolution. Biochemistry 2017, 56: 5194-5201. PMID: 28792749, PMCID: PMC5854879, DOI: 10.1021/acs.biochem.7b00545.Peer-Reviewed Original ResearchConceptsLive cellsOrganelle dynamicsDiscrete organellesMultiple organellesLive-cell nanoscopyPlasma membraneDiverse processesEndoplasmic reticulumDynamic assemblyLiving cellsDynamic reorganizationOrganellesSingle-molecule switchingMembrane probeCellsMembraneMitochondriaReticulumRegulationHigh densityProbeAssemblyNew toolkitLong time periodsDivisionLong‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR
Thompson AD, Omar MH, Rivera‐Molina F, Xi Z, Koleske AJ, Toomre DK, Schepartz A. Long‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR. Angewandte Chemie International Edition 2017, 56: 10408-10412. PMID: 28679029, PMCID: PMC5576494, DOI: 10.1002/anie.201704783.Peer-Reviewed Original ResearchLong time-lapse nanoscopy with spontaneously blinking membrane probes
Takakura H, Zhang Y, Erdmann RS, Thompson AD, Lin Y, McNellis B, Rivera-Molina F, Uno SN, Kamiya M, Urano Y, Rothman JE, Bewersdorf J, Schepartz A, Toomre D. Long time-lapse nanoscopy with spontaneously blinking membrane probes. Nature Biotechnology 2017, 35: 773-780. PMID: 28671662, PMCID: PMC5609855, DOI: 10.1038/nbt.3876.Peer-Reviewed Original ResearchExcess 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 diabetesA novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi
Bottanelli F, Kilian N, Ernst AM, Rivera-Molina F, Schroeder LK, Kromann EB, Lessard MD, Erdmann RS, Schepartz A, Baddeley D, Bewersdorf J, Toomre D, Rothman JE. A novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi. Molecular Biology Of The Cell 2017, 28: 1676-1687. PMID: 28428254, PMCID: PMC5469610, DOI: 10.1091/mbc.e16-12-0863.Peer-Reviewed Original ResearchDifferential 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