2023
Nucleolar structure connects with global nuclear organization.
Wang C, Ma H, Baserga S, Pederson T, Huang S. Nucleolar structure connects with global nuclear organization. Molecular Biology Of The Cell 2023, 34: ar114. PMID: 37610836, PMCID: PMC10846622, DOI: 10.1091/mbc.e23-02-0062.Peer-Reviewed Original ResearchConceptsNucleolar structureGenomic lociNuclear domainsSpecific genomic lociGlobal nuclear organizationRNA processing factorsRNA polymerase ICajal bodiesNuclear organizationRibosome synthesisNuclear bodiesKnockdown cellsPerinucleolar compartmentPolymerase IIntranuclear locationHeLa cellsNucleolar segregationSpatial organizationNucleoliLociUtp4CellsRPA194SegregationCompositional changes
2022
In situ architecture of the lipid transport protein VPS13C at ER–lysosome membrane contacts
Cai S, Wu Y, Guillén-Samander A, Hancock-Cerutti W, Liu J, De Camilli P. In situ architecture of the lipid transport protein VPS13C at ER–lysosome membrane contacts. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203769119. PMID: 35858323, PMCID: PMC9303930, DOI: 10.1073/pnas.2203769119.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumCryo-focused ion beam millingMembrane contact sitesCryo-electron tomographyFull-length structureLipid transport proteinsRod-like densitiesLysosome contactBinding partnerGenetic approachesHydrophobic grooveTransport proteinsContact sitesVps13Lipid transportAlphaFold predictionsFull-length modelHeLa cellsMembrane contactSitu architectureAdjacent membranesVPS13CProteinStructural informationEndo/lysosomesRestricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment
Rajendran M, Queralt-Martín M, Gurnev P, Rosencrans W, Rovini A, Jacobs D, Abrantes K, Hoogerheide D, Bezrukov S, Rostovtseva T. Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment. Cellular And Molecular Life Sciences 2022, 79: 368. PMID: 35718804, PMCID: PMC11072225, DOI: 10.1007/s00018-022-04389-w.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelVDAC poreProtein-membrane bindingRegulating mitochondrial functionProximity ligation assayInvolvement of alpha-synucleinMembrane bindingMitochondrial respirationMitochondrial functionHeLa cellsLigation assayLipid membranesHexokinase 2MitochondriaTranslocation processComplex inhibitionAnion channelFluorescence correlation spectroscopyAlpha-synucleinMolecular levelMitochondrial toxicityASynTranslocationPeptide therapeuticsTherapeutic targetLymphocyte Cytosolic Protein 1 (L-plastin) I232F Mutation Impairs Granulocytic Proliferation and Causes Neutropenia
Mahat U, Garg B, Yang CY, Mehta H, Hanna R, Rogers HJ, Flagg A, Ivanov AI, Corey SJ. Lymphocyte Cytosolic Protein 1 (L-plastin) I232F Mutation Impairs Granulocytic Proliferation and Causes Neutropenia. Blood Advances 2022, 6: 2581-2594. PMID: 34991157, PMCID: PMC9043934, DOI: 10.1182/bloodadvances.2021006398.Peer-Reviewed Original ResearchConceptsLymphocyte cytosolic protein 1Impaired cell motilityDiffuse intracellular localizationUnfolded protein responseCytosolic protein 1Level of genesCell cycle arrestActin regulationG2/M phaseNew genesActin cytoskeletonActin dynamicsCell motilityProtein responseSubcellular fractionationMutant formsF-actinIntracellular localizationWhole-exome sequencingCycle arrestHeLa cellsMissense mutationsHeterozygous missense mutationM phaseLCP1Pathogenic Leptospira Evolved a Unique Gene Family Comprised of Ricin B-Like Lectin Domain-Containing Cytotoxins
Chaurasia R, Marroquin AS, Vinetz JM, Matthias MA. Pathogenic Leptospira Evolved a Unique Gene Family Comprised of Ricin B-Like Lectin Domain-Containing Cytotoxins. Frontiers In Microbiology 2022, 13: 859680. PMID: 35422779, PMCID: PMC9002632, DOI: 10.3389/fmicb.2022.859680.Peer-Reviewed Original ResearchVM proteinsUnique gene familiesStructural homology searchRecombinant ricin B chainΒ-trefoil domainR-type lectinsCaspase-3 activationHeLa cell surfaceBacterial plasmid DNAGene familyImportant virulence determinantN-terminal fragmentHomology searchCell surface bindingRicin B chainHuman cellsNuclear fragmentationB domainHeLa cellsCell surfaceNuclear translocationVirulence determinantsDNase activityDNase functionProtein
2021
Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells
Song JE, Alves TC, Stutz B, Šestan-Peša M, Kilian N, Jin S, Diano S, Kibbey RG, Horvath TL. Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells. Metabolites 2021, 11: 322. PMID: 34069800, PMCID: PMC8157282, DOI: 10.3390/metabo11050322.Peer-Reviewed Original ResearchExogenous fatty acidsMitochondrial fissionMitochondrial fatty acid oxidationFatty acid oxidationFatty acid usageMitochondrial morphologyLipid dropletsAcid usageCarnitine palmitoyltransferase 1HeLa cellsDynamin-related proteinKey mitochondrial proteinsFatty acidsAcid oxidationMitochondrial proteinsLipid droplet accumulationMitochondrial dynamicsNovel functionLipid homeostasisHigh abundanceDirect roleDroplet accumulationMitochondriaFatty acid contentProteinRetention Using Selective Hooks (RUSH) Cargo Sorting Assay for Live-cell Vesicle Tracking in the Secretory Pathway Using HeLa Cells.
Pakdel M, Pacheco-Fernandez N, von Blume J. Retention Using Selective Hooks (RUSH) Cargo Sorting Assay for Live-cell Vesicle Tracking in the Secretory Pathway Using HeLa Cells. Bio-protocol 2021, 11: e3958. PMID: 33855118, PMCID: PMC8032492, DOI: 10.21769/bioprotoc.3958.Peer-Reviewed Original ResearchProtein traffickingVesicle traffickingSecretory pathwayGolgi vesicle traffickingSelective hooks (RUSH) systemHeLa cellsLive-cell microscopyMammalian cellsProtein cargoLive-cell monitoringCargo vesiclesVesicle trackingTraffickingRUSH systemSorting assaysWide-field microscopyPhysiological conditionsVesiclesMore detail processesPathwayCargoCellsFinal destinationProteinSecretoryRetention Using Selective Hooks (RUSH) Cargo Sorting Assay for Protein Vesicle Tracking in HeLa Cells.
Pacheco-Fernandez N, Pakdel M, Von Blume J. Retention Using Selective Hooks (RUSH) Cargo Sorting Assay for Protein Vesicle Tracking in HeLa Cells. Bio-protocol 2021, 11: e3936. PMID: 33796610, PMCID: PMC8005885, DOI: 10.21769/bioprotoc.3936.Peer-Reviewed Original ResearchSecretory pathwaySelective hooks (RUSH) systemProtein sortingVesicle traffickingSpecific cargoCargo traffickingProtein cargoTrafficking dynamicsProtein dynamicsVesicle trackingBiotin additionHeLa cellsFluorescent vesiclesTraffickingSorting assaysPathwayCargoCellsProteinExcellent toolSuch studiesVesiclesBetter understandingRegulationSorting
2020
Dependence of fluorodeoxyglucose (FDG) uptake on cell cycle and dry mass: a single-cell study using a multi-modal radiography platform
Sung Y, Tetrault M, Takahashi K, Ouyang J, Pratx G, Fakhri G, Normandin M. Dependence of fluorodeoxyglucose (FDG) uptake on cell cycle and dry mass: a single-cell study using a multi-modal radiography platform. Scientific Reports 2020, 10: 4280. PMID: 32152343, PMCID: PMC7062696, DOI: 10.1038/s41598-020-59515-0.Peer-Reviewed Original ResearchConceptsCell divisionHeLa cellsDry massM phaseCell dry massCancer compared to normal tissuesCell cycle phasesHouse-keeping proteinsSingle-cell studiesSingle-cell levelIncreased dry massProliferation indexCell cycleG1 phaseProportion of cellsHigher glucose uptakeFluorodeoxyglucose uptakeGlucose uptakeHeLaUptake rate
2019
H2A.Z facilitates licensing and activation of early replication origins
Long H, Zhang L, Lv M, Wen Z, Zhang W, Chen X, Zhang P, Li T, Chang L, Jin C, Wu G, Wang X, Yang F, Pei J, Chen P, Margueron R, Deng H, Zhu M, Li G. H2A.Z facilitates licensing and activation of early replication origins. Nature 2019, 577: 576-581. PMID: 31875854, DOI: 10.1038/s41586-019-1877-9.Peer-Reviewed Original ResearchConceptsOrigin recognition complexHistone variant H2A.ZEarly replication originsReplication originsVariant H2A.ZReplication timingChromatin-based regulatory mechanismsEarly replication timingGenome-wide studiesNascent DNA strandsH2A.Z resultsNucleosome bindsDNA replicationH2A.ZHistone H4Cell cycle1Precise duplicationRegulated processDNA sequencesRegulatory mechanismsHeLa cellsDNA strandsORC1Firing efficiencyGenomeLACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes
Huang C, Hedl M, Ranjan K, Abraham C. LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes. Cell Reports 2019, 29: 4525-4539.e4. PMID: 31875558, PMCID: PMC7372507, DOI: 10.1016/j.celrep.2019.11.105.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 6eIF-2 KinaseEndoplasmic ReticulumEndoplasmic Reticulum StressEndoribonucleasesEnterococcus faecalisEscherichia coliGene Expression RegulationHeLa CellsHost-Pathogen InteractionsHumansImmunity, InnateIntracellular Signaling Peptides and ProteinsMacrophagesNod2 Signaling Adaptor ProteinPhagocytosisPrimary Cell CultureProtein Serine-Threonine KinasesRiskSignal TransductionConceptsEndoplasmic reticulumER stressER stress sensorsHuman macrophagesInnate immune outcomesDisease risk variantsMultiple immune-mediated diseasesLaccase domainPattern recognition receptor NOD2HeLa cellsAntimicrobial pathwaysRisk variantsGenetic variantsLACC1Critical roleVariantsMacrophagesATF6IRE1αArg284SignalingReticulumStressTransfectionPERKIL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes
Sun R, Hedl M, Abraham C. IL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes. Gut 2019, 69: 264-273. PMID: 31097538, PMCID: PMC6858485, DOI: 10.1136/gutjnl-2018-316830.Peer-Reviewed Original ResearchConceptsMonocyte-derived macrophagesHuman monocyte-derived macrophagesJanus kinase/signal transducerKinase/signal transducerDynamin-mediated endocytosisReceptor-induced signalingCell surface regulationR381Q variantIBD pathogenesisIntestinal myeloid cellsLate endosomesPattern recognition receptorsSignal transducerPathway membersDefines mechanismsReal-time PCRCell typesHeLa cellsSignalingKey playersRNA expressionHuman macrophagesPathwayWestern blotMyeloid cellsMulti-omic measurements of heterogeneity in HeLa cells across laboratories
Liu Y, Mi Y, Mueller T, Kreibich S, Williams EG, Van Drogen A, Borel C, Frank M, Germain PL, Bludau I, Mehnert M, Seifert M, Emmenlauer M, Sorg I, Bezrukov F, Bena FS, Zhou H, Dehio C, Testa G, Saez-Rodriguez J, Antonarakis SE, Hardt WD, Aebersold R. Multi-omic measurements of heterogeneity in HeLa cells across laboratories. Nature Biotechnology 2019, 37: 314-322. PMID: 30778230, DOI: 10.1038/s41587-019-0037-y.Peer-Reviewed Original ResearchConceptsCell linesGenome-wide copy numberMulti-omic measurementsHuman cultured cellsProtein turnover ratesPhenotypic responsesGenomic variabilityDifferent cell linesHeLa variantsSpecific cell linesCopy numberHeLa cellsCultured cellsHeLa cell linePhenotypic variabilityProgressive divergenceTurnover rateCellsBiological variationTechnical variationUniform conditionsTranscriptomeProteomeSuccessive passagesLines
2017
Cellular differentiation state modulates the mRNA export activity of SR proteins
Botti V, McNicoll F, Steiner MC, Richter FM, Solovyeva A, Wegener M, Schwich OD, Poser I, Zarnack K, Wittig I, Neugebauer KM, Müller-McNicoll M. Cellular differentiation state modulates the mRNA export activity of SR proteins. Journal Of Cell Biology 2017, 216: 1993-2009. PMID: 28592444, PMCID: PMC5496613, DOI: 10.1083/jcb.201610051.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsArginineCell DifferentiationCell NucleusDNA-Binding ProteinsHeLa CellsHumansImmunoprecipitationMethylationMiceNeurogenesisPhenotypePhosphorylationPluripotent Stem CellsProtein BindingProtein Processing, Post-TranslationalRepressor ProteinsRNA InterferenceRNA-Binding ProteinsRNA, MessengerSerine-Arginine Splicing FactorsTandem Mass SpectrometryTranscription FactorsTransfectionConceptsMRNA export activitySR proteinsP19 cellsMRNA exportSR protein family membersProtein-RNA interactionsMurine P19 cellsCellular differentiation stateProtein family membersLower phosphorylation levelsArginine methylationPluripotency factorsCytoplasmic mRNA levelsMRNA processingPosttranslational modificationsCellular dynamicsDifferentiated cellsNeural differentiationSRSF5Differentiation statePhosphorylation levelsHeLa cellsProteinExport activityMRNA levelsSettling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover
Rosa-Mercado NA, Withers JB, Steitz JA. Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover. Genes & Development 2017, 31: 957-958. PMID: 28637691, PMCID: PMC5495124, DOI: 10.1101/gad.302695.117.Peer-Reviewed Original ResearchConceptsPre-mRNA splicing eventsPost-transcriptional modificationsMRNA biogenesisDifferent subcellular fractionsMRNA biologySplicing eventsMature mRNABiochemical approachesRNA transcriptsPivotal regulatorMethylation levelsHeLa cellsSubcellular fractionsRNA nucleosidesMethylationTranscriptsBiogenesisChromatinSplicingMethyladenosineExonsGenesRNABiologyRegulatorDifferential 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
2016
Control of serotonin transporter phosphorylation by conformational state
Zhang YW, Turk BE, Rudnick G. Control of serotonin transporter phosphorylation by conformational state. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e2776-e2783. PMID: 27140629, PMCID: PMC4878475, DOI: 10.1073/pnas.1603282113.Peer-Reviewed Original ResearchConceptsTransmembrane helix 5Cytoplasmic permeation pathwaysOutward open conformationIntact rat basophilic leukemia cellsCGMP-dependent phosphorylationInhibition of phosphorylationTM5 helicesTransporter phosphorylationSERT regulationOutward openingCysteine residuesHelix 5Open conformationCytoplasmic endHuman SERTPhosphorylationPermeation pathwayConformational statesHeLa cellsRat basophilic leukemia cellsBasophilic leukemia cellsSERT activityExocytotic releaseLeukemia cellsMutations
2015
The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy
Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW. The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy. Molecular Cell 2015, 60: 7-20. PMID: 26365381, PMCID: PMC4592482, DOI: 10.1016/j.molcel.2015.08.016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell Cycle ProteinsHeLa CellsHumansMembrane Transport ProteinsMitochondriaMitophagyNuclear ProteinsPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProteomicsSequestosome-1 ProteinTranscription Factor TFIIIAUbiquitin-Protein LigasesUbiquitinationConceptsUbiquitin chainsEfficient mitophagyTBK1 activationPINK1-Parkin pathwayUbiquitylation pathwayAdaptor recruitmentCellular homeostasisMitochondrial retentionTBK1 kinaseDamaged mitochondriaChain bindingMitophagyHeLa cellsMitochondriaPhosphorylationNDP52Positive feedback mechanismPathwayOPTNRecruitmentActivationAmyotrophic lateral sclerosisAssemblyS473Kinase
2014
Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting
Kienzle C, Basnet N, Crevenna AH, Beck G, Habermann B, Mizuno N, von Blume J. Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting. Journal Of Cell Biology 2014, 206: 635-654. PMID: 25179631, PMCID: PMC4151145, DOI: 10.1083/jcb.201311052.Peer-Reviewed Original ResearchMembrane adhesion dictates Golgi stacking and cisternal morphology
Lee I, Tiwari N, Dunlop MH, Graham M, Liu X, Rothman JE. Membrane adhesion dictates Golgi stacking and cisternal morphology. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 1849-1854. PMID: 24449908, PMCID: PMC3918774, DOI: 10.1073/pnas.1323895111.Peer-Reviewed Original ResearchConceptsFK506-binding protein (FKBP) domainsGolgi cisternaeGolgi matrix proteinsClass of proteinsCisternal morphologyCisternal maturationProtein domainsGolgi membranesGolgi stacksRegulatory proteinsGolgiMatrix proteinsMembrane adhesionMembrane transportProtein 55Adhesive processHeLa cellsAdhesive proteinsProteinGolginsCargo transportAncient formCisternaeQuantitative electron microscopyMitochondria
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