2023
PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
Xu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.Peer-Reviewed Original ResearchConceptsC-terminal β-barrel domainSpike-mediated fusionCell-autonomous defenseLarge-scale exome sequencingΒ-barrel domainGenome-wide CRISPRSARS-CoV-2 infectionHost cell cytosolScramblase activityPhospholipid scramblaseLive SARS-CoV-2 infectionHuman lung epitheliumPLSCR1SARS-CoV-2 USASingle-molecule switchingSARS-CoV-2 variantsExome sequencingHuman populationRestriction factorsViral RNANew SARS-CoV-2 variantsSARS-CoV-2Robust activityLung epitheliumDefense factors
2021
A human apolipoprotein L with detergent-like activity kills intracellular pathogens
Gaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ, Huang S, Xu D, Mamiñska A, Nguyen TN, Lazarou M, Karatekin E, Gupta K, MacMicking JD. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science 2021, 373 PMID: 34437126, PMCID: PMC8422858, DOI: 10.1126/science.abf8113.Peer-Reviewed Original ResearchMeSH KeywordsApolipoproteins LBacterial Outer MembraneBacteriolysisCell MembraneCell Membrane PermeabilityCells, CulturedCRISPR-Cas SystemsCytosolDetergentsGene EditingGram-Negative BacteriaGTP-Binding ProteinsHumansImmunity, InnateInterferon-gammaLipoproteinsMicrobial ViabilityO AntigensProtein DomainsSalmonella typhimuriumSolubilityConceptsSingle-particle cryo-electron microscopyCell-autonomous defenseCytosol-invasive bacteriaExpression of hundredsNative mass spectrometryCryo-electron microscopyHuman genesDetergent-like activityHost proteinsLipoprotein nanodiscsMammalian lipidsExtracellular transportImmune cytokine interferonCell typesDetergent-like propertiesApolipoprotein LLife-threatening infectionsPotent bactericidal agentsAnionic membranesProteinCytokine interferonNonimmune cellsMass spectrometryCellsMutagenesisThe neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores
Wu Z, Dharan N, McDargh ZA, Thiyagarajan S, O'Shaughnessy B, Karatekin E. The neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores. ELife 2021, 10: e68215. PMID: 34190041, PMCID: PMC8294851, DOI: 10.7554/elife.68215.Peer-Reviewed Original Research
2020
Retromer forms low order oligomers on supported lipid bilayers
Deatherage CL, Nikolaus J, Karatekin E, Burd CG. Retromer forms low order oligomers on supported lipid bilayers. Journal Of Biological Chemistry 2020, 295: 12305-12316. PMID: 32651229, PMCID: PMC7443500, DOI: 10.1074/jbc.ra120.013672.Peer-Reviewed Original ResearchConceptsLow-order oligomersAccessory factorsLipid bilayersMembrane-associated cargoesCoat protein complexIntegral membrane proteinsModel cargo proteinSingle-particle fluorescence microscopyRetromer sorting pathwayMembrane cargoNexin 3WASH complexCargo proteinsSorting pathwaysMembrane associationProtein complexesSNX3-retromerEndosomal systemMembrane proteinsEndosome membraneRecycling pathwayRetromerOligomeric interactionsIntrinsic propensityFluorescence microscopy
2019
Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment
Ren C, Yuan Q, Braun M, Zhang X, Petri B, Zhang J, Kim D, Guez-Haddad J, Xue W, Pan W, Fan R, Kubes P, Sun Z, Opatowsky Y, Polleux F, Karatekin E, Tang W, Wu D. Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment. Developmental Cell 2019, 49: 206-219.e7. PMID: 30930167, PMCID: PMC6482112, DOI: 10.1016/j.devcel.2019.02.023.Peer-Reviewed Original ResearchActinsAnimalsCell AdhesionCell MembraneCell MovementCell PolarityCell-Matrix JunctionsCytoskeletonEndotheliumFemaleGTPase-Activating ProteinsHEK293 CellsHumansLeukocytesMaleMiceMice, Inbred C57BLMice, KnockoutMinor Histocompatibility AntigensMyosin Light ChainsNeutrophilsPhosphatidylinositol PhosphatesPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Signal Transduction
2018
Toward a unified picture of the exocytotic fusion pore
Karatekin E. Toward a unified picture of the exocytotic fusion pore. FEBS Letters 2018, 592: 3563-3585. PMID: 30317539, PMCID: PMC6353554, DOI: 10.1002/1873-3468.13270.Peer-Reviewed Original Research
2017
Dilation of fusion pores by crowding of SNARE proteins
Wu Z, Bello OD, Thiyagarajan S, Auclair SM, Vennekate W, Krishnakumar SS, O'Shaughnessy B, Karatekin E. Dilation of fusion pores by crowding of SNARE proteins. ELife 2017, 6: e22964. PMID: 28346138, PMCID: PMC5404929, DOI: 10.7554/elife.22964.Peer-Reviewed Original Research
2016
Nanodisc-cell fusion: control of fusion pore nucleation and lifetimes by SNARE protein transmembrane domains
Wu Z, Auclair SM, Bello O, Vennekate W, Dudzinski NR, Krishnakumar SS, Karatekin E. Nanodisc-cell fusion: control of fusion pore nucleation and lifetimes by SNARE protein transmembrane domains. Scientific Reports 2016, 6: 27287. PMID: 27264104, PMCID: PMC4893671, DOI: 10.1038/srep27287.Peer-Reviewed Original ResearchConceptsFusion poreTransmembrane domainPore dynamicsProtein transmembrane domainNeurotransmitter-filled vesiclesT-SNAREsPlasma membraneRecycling kineticsPore lifetimePore currentsFlickering poresPore stabilityMultiple timesZipperingNanodiscsDomainProteinVesiclesMembraneCellsAssaysCognatesPore propertiesPores
2010
A fast, single-vesicle fusion assay mimics physiological SNARE requirements
Karatekin E, Di Giovanni J, Iborra C, Coleman J, O'Shaughnessy B, Seagar M, Rothman JE. A fast, single-vesicle fusion assay mimics physiological SNARE requirements. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 3517-3521. PMID: 20133592, PMCID: PMC2840481, DOI: 10.1073/pnas.0914723107.Peer-Reviewed Original Research
2004
The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging
Zecca L, Stroppolo A, Gatti A, Tampellini D, Toscani M, Gallorini M, Giaveri G, Arosio P, Santambrogio P, Fariello R, Karatekin E, Kleinman M, Turro N, Hornykiewicz O, Zucca F. The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 9843-9848. PMID: 15210960, PMCID: PMC470762, DOI: 10.1073/pnas.0403495101.Peer-Reviewed Original ResearchConceptsSubstantia nigraLocus coeruleusLC neuronsNeuronal vulnerabilityParkinson's diseaseCopper/zinc SODZinc SODCompacta neuronsParkinsonian syndromesBrainstem nucleiManganese superoxide dismutaseGlial cellsMajor molecular formCeruloplasmin levelsNormal subjectsRelated disordersRole of ironLight chain ferritinNeuronsDiseaseManganese SODFerritinNeuromelaninCoeruleusNM concentrations