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 relationshipsImagesThroughput
2019
Labeling 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
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
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 miceNovel 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 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 diabetes
2016
Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation
Zhou HJ, Qin L, Zhang H, Tang W, Ji W, He Y, Liang X, Wang Z, Yuan Q, Vortmeyer A, Toomre D, Fuh G, Yan M, Kluger MS, Wu D, Min W. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nature Medicine 2016, 22: 1033-1042. PMID: 27548575, PMCID: PMC5014607, DOI: 10.1038/nm.4169.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1Angiopoietin-2AnimalsApoptosis Regulatory ProteinsBrainEndothelium, VascularEnzyme-Linked Immunosorbent AssayExocytosisFluorescent Antibody TechniqueGene Expression ProfilingHemangioma, Cavernous, Central Nervous SystemHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNerve Tissue ProteinsProto-Oncogene ProteinsReceptor, TIE-2Vesicle-Associated Membrane Protein 3Ultra-High Resolution 3D Imaging of Whole Cells
Huang F, Sirinakis G, Allgeyer ES, Schroeder LK, Duim WC, Kromann EB, Phan T, Rivera-Molina FE, Myers JR, Irnov I, Lessard M, Zhang Y, Handel MA, Jacobs-Wagner C, Lusk CP, Rothman JE, Toomre D, Booth MJ, Bewersdorf J. Ultra-High Resolution 3D Imaging of Whole Cells. Cell 2016, 166: 1028-1040. PMID: 27397506, PMCID: PMC5005454, DOI: 10.1016/j.cell.2016.06.016.Peer-Reviewed Original ResearchConceptsCell biological researchResolution 3D imagingHigh-resolution 3D imagingOptical nanoscopeSuper-resolution microscopyThree-dimensional structureMammalian cellsNuclear poresSynaptonemal complexFluorescence nanoscopyThick samplesThin samplesBiological researchNanoscopyInferior resolutionCellular volumeWhole cellsDepth directionMolecular architecturePractical biological applicationsBiological applicationsComplex molecular architecturesResolutionNanoscopeCellsOptogenetic 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 cellsVesiclesPathwayCIB1PIP3CellsTwo-colour live-cell nanoscale imaging of intracellular targets
Bottanelli F, Kromann EB, Allgeyer ES, Erdmann RS, Wood Baguley S, Sirinakis G, Schepartz A, Baddeley D, Toomre DK, Rothman JE, Bewersdorf J. Two-colour live-cell nanoscale imaging of intracellular targets. Nature Communications 2016, 7: 10778. PMID: 26940217, PMCID: PMC4785223, DOI: 10.1038/ncomms10778.Peer-Reviewed Original Research
2015
The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135
Stoops EH, Hull M, Olesen C, Mistry K, Harder JL, Rivera-Molina F, Toomre D, Caplan MJ. The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135. Journal Of Cell Biology 2015, 211: 287-294. PMID: 26504168, PMCID: PMC4621837, DOI: 10.1083/jcb.201502045.Peer-Reviewed Original ResearchConceptsPrimary ciliaSurface proteinsTrans-Golgi networkPolarized epithelial cellsApical surface proteinsSNAP-tag systemBasolateral plasma membraneCell surface proteinsEpithelial cellsApical proteinsPericiliary regionGolgi networkPolarized traffickingCarrier vesiclesProtein deliveryPlasma membraneApical membraneProteinGp135Basolateral membraneCiliaMembraneHot spotsCellsTrafficking
2014
Reticulon 4 Is Necessary for Endoplasmic Reticulum Tubulation, STIM1-Orai1 Coupling, and Store-operated Calcium Entry
Jozsef L, Tashiro K, Kuo A, Park EJ, Skoura A, Albinsson S, Rivera-Molina F, Harrison KD, Iwakiri Y, Toomre D, Sessa WC. Reticulon 4 Is Necessary for Endoplasmic Reticulum Tubulation, STIM1-Orai1 Coupling, and Store-operated Calcium Entry. Journal Of Biological Chemistry 2014, 289: 9380-9395. PMID: 24558039, PMCID: PMC3969502, DOI: 10.1074/jbc.m114.548602.Peer-Reviewed Original ResearchConceptsSTIM1-Orai1 couplingER morphologyRedistribution of STIM1Store-operated calcium entryER tubulationER sheetsElevated cytoplasmicReticulon 4Functional consequencesRTN4SOCETubulationCalcium entryRecent advancesFundamental questionsSTIM1CytoplasmicHomeostasisApoptosisRegulationMechanisticallyFirst timeCellsMorphology
2013
A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils
Zhang Y, Tang W, Zhang H, Niu X, Xu Y, Zhang J, Gao K, Pan W, Boggon TJ, Toomre D, Min W, Wu D. A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils. Developmental Cell 2013, 27: 215-226. PMID: 24176643, PMCID: PMC3834565, DOI: 10.1016/j.devcel.2013.09.021.Peer-Reviewed Original ResearchConceptsNeutrophil degranulationAcute innate immune responseIschemia-reperfusion injuryInnate immune responseProtection of kidneyNeutrophil functionImmune responseInhibition of exocytosisTissue damageGranule poolGranule contentsDegranulationImportant regulatorImportant roleVesicle exocytosisExocytosisSTK24InjuryNeutrophilsKidneyUNC13DThe 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 componentsCaveolae, Fenestrae and Transendothelial Channels Retain PV1 on the Surface of Endothelial Cells
Tkachenko E, Tse D, Sideleva O, Deharvengt SJ, Luciano MR, Xu Y, McGarry CL, Chidlow J, Pilch PF, Sessa WC, Toomre DK, Stan RV. Caveolae, Fenestrae and Transendothelial Channels Retain PV1 on the Surface of Endothelial Cells. PLOS ONE 2012, 7: e32655. PMID: 22403691, PMCID: PMC3293851, DOI: 10.1371/journal.pone.0032655.Peer-Reviewed Original ResearchConceptsFormation of diaphragmsRemoval of caveolaeDynamin-independent pathwayAbsence of caveolaeEndothelial cellsProtein levelsCellular rolesCavin-1Knockout phenotypesPlasma membraneCaveolin-1CaveolaeLung endothelial cellsCell surfaceRapid internalizationInternalization rateAbundance of structuresMice resultsTransendothelial channelsEssential componentOnly roleFenestral diaphragmsCellsClathrinTranscription
2011
Using light to see and control membrane traffic
Xu Y, Melia TJ, Toomre DK. Using light to see and control membrane traffic. Current Opinion In Chemical Biology 2011, 15: 822-830. PMID: 22079055, DOI: 10.1016/j.cbpa.2011.10.016.Peer-Reviewed Original ResearchDual-mode of insulin action controls GLUT4 vesicle exocytosis
Xu Y, Rubin BR, Orme CM, Karpikov A, Yu C, Bogan JS, Toomre DK. Dual-mode of insulin action controls GLUT4 vesicle exocytosis. Journal Of Cell Biology 2011, 193: 643-653. PMID: 21555461, PMCID: PMC3166865, DOI: 10.1083/jcb.201008135.Peer-Reviewed Original ResearchMeSH Keywords3T3-L1 CellsAdipocytesAnimalsBiosensing TechniquesCarrier ProteinsExocytosisGlucose Transporter Type 4Green Fluorescent ProteinsInsulinIntracellular Signaling Peptides and ProteinsKineticsMembrane FusionMiceMicroscopy, FluorescenceMicroscopy, VideoPhospholipase DRecombinant Fusion ProteinsRNA InterferenceTransfectionTransport VesiclesVesicle-Associated Membrane Protein 2ConceptsGLUT4 storage vesiclesVesicle exocytosisInsulin-stimulated control cellsGLUT4 vesicle exocytosisPlasma membrane fusionNovel regulatory siteSingle vesicle exocytosisInsulin triggersVesicle trafficExocytic rateFusion poreSurface of adipocytesMembrane fusionRegulatory sitesPhospholipase DStorage vesiclesPore expansionExocytosisControl cellsAcute perturbationVesiclesInsulin actionVesicle characteristicsAdipocytesCellsExocyst function regulated by effector phosphorylation
Chen XW, Leto D, Xiao J, Goss J, Wang Q, Shavit JA, Xiong T, Yu G, Ginsburg D, Toomre D, Xu Z, Saltiel AR. Exocyst function regulated by effector phosphorylation. Nature Cell Biology 2011, 13: 580-588. PMID: 21516108, PMCID: PMC3904505, DOI: 10.1038/ncb2226.Peer-Reviewed Original ResearchConceptsInsulin-stimulated GLUT4 exocytosisProtein kinase CGLUT4 vesiclesExocyst functionGLUT4 exocytosisUndergoes phosphorylationExocytic vesiclesPhosphorylation eventsContinuous exocytosisSmall GTPasesPhosphorylation sitesZebrafish embryosTrafficking processesBinding domainsSite of fusionEffector phosphorylationExocystBearing mutationsKinase CG proteinsPhosphorylationVesiclesRalAEpithelial cellsExocytosis