2024
Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB
Lampson B, Ramίrez A, Baro M, He L, Hegde M, Koduri V, Pfaff J, Hanna R, Kowal J, Shirole N, He Y, Doench J, Contessa J, Locher K, Kaelin W. Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB. Cell 2024, 187: 2209-2223.e16. PMID: 38670073, PMCID: PMC11149550, DOI: 10.1016/j.cell.2024.03.022.Peer-Reviewed Original ResearchConceptsWhole-genome CRISPR-Cas9 screenCRISPR-Cas9 screensCryoelectron microscopy studiesCell surface localizationLipopolysaccharide receptor Toll-like receptor 4OST complexToll-like receptor 4CRISPR screensNF-kBCatalytic subunitN-glycosylationActivate NF-kBBase editorsUncompetitive inhibition mechanismNGI-1Molecular mechanismsCatalytic siteLPS-treated cellsOligosaccharyltransferaseDruggable pocketSTT3AReceptor Toll-like receptor 4Drug mechanism of actionStructural studiesInflammatory signaling
2023
Scalable production of tissue-like vascularized liver organoids from human PSCs
Harrison S, Siller R, Tanaka Y, Chollet M, de la Morena-Barrio M, Xiang Y, Patterson B, Andersen E, Bravo-Pérez C, Kempf H, Åsrud K, Lunov O, Dejneka A, Mowinckel M, Stavik B, Sandset P, Melum E, Baumgarten S, Bonanini F, Kurek D, Mathapati S, Almaas R, Sharma K, Wilson S, Skottvoll F, Boger I, Bogen I, Nyman T, Wu J, Bezrouk A, Cizkova D, Corral J, Mokry J, Zweigerdt R, Park I, Sullivan G. Scalable production of tissue-like vascularized liver organoids from human PSCs. Experimental & Molecular Medicine 2023, 55: 2005-2024. PMID: 37653039, PMCID: PMC10545717, DOI: 10.1038/s12276-023-01074-1.Peer-Reviewed Original ResearchConceptsExtracellular matrixSingle-cell RNA sequencingBasic developmental biologyEmbryonic liver developmentPost-translational modificationsLiver-like functionsCostly growth factorsOrganoid modelsKey liver functionsCellular diversityCellular repertoireDevelopmental biologyCellular complexityN-glycosylationRNA sequencingDe novo vascularizationNumber of tissuesProtein productionSerum protein productionLiver developmentHuman PSCsDrug toxicity assessmentOrganoidsSmall moleculesGrowth factorSignal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation
Phoomak C, Rinis N, Baro M, Shrimal S, Bennett D, Shaffer S, Lehrman M, Gilmore R, Contessa J. Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation. Science Advances 2023, 9: eade8079. PMID: 36921042, PMCID: PMC10017033, DOI: 10.1126/sciadv.ade8079.Peer-Reviewed Original ResearchConceptsSignal recognition particle receptorN-glycosylationProper protein foldingCotranslational N-glycosylationOligosaccharyltransferase complexPosttranslational modificationsProtein foldingSecretory compartmentsHigh-throughput screeningEndoplasmic reticulumCellular localizationUnrecognized functionChemical probesProteinTransloconReceptorsSubunitsFoldingReticulumMutationsPhenotypeCompartmentsAssemblyCellsLocalization
2021
The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress
Phoomak C, Cui W, Hayman TJ, Yu SH, Zhao P, Wells L, Steet R, Contessa JN. The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress. Science Advances 2021, 7: eabc6364. PMID: 33523898, PMCID: PMC7810369, DOI: 10.1126/sciadv.abc6364.Peer-Reviewed Original ResearchTranslocon-associated proteinN-glycosylationER stressER glycoprotein quality controlTranslocon-associated protein complexEndoplasmic reticulum (ER) homeostasisAberrant N-glycosylationGlycoprotein quality controlER chaperone BiPFluorescence-based strategyProtein complexesPosttranslational modificationsChaperone BiPTRAP complexGlycosylation defectsConditions of stressRegulatory roleTranscriptional signatureIndividual cellsDownstream ERProtein levelsSubunitsSSR3GlycosylationCells
2020
The N-glycome regulates the endothelial-to-hematopoietic transition
Kasper DM, Hintzen J, Wu Y, Ghersi JJ, Mandl HK, Salinas KE, Armero W, He Z, Sheng Y, Xie Y, Heindel DW, Park EJ, Sessa WC, Mahal LK, Lebrilla C, Hirschi KK, Nicoli S. The N-glycome regulates the endothelial-to-hematopoietic transition. Science 2020, 370: 1186-1191. PMID: 33273096, PMCID: PMC8312266, DOI: 10.1126/science.aaz2121.Peer-Reviewed Original ResearchMeSH KeywordsADAM10 ProteinAnimalsAnimals, Genetically Modifiedbeta-Galactoside alpha-2,3-SialyltransferaseCell LineageCell TransdifferentiationEndothelial CellsGenes, ReporterGlycomicsGlycoproteinsGlycosylationHematopoietic Stem CellsMannosyltransferasesMicroRNAsPolysaccharidesSialyltransferasesZebrafishConceptsHematopoietic transitionHemogenic endothelial cellsProtein N-glycosylationLymphoid-myeloid lineageN-glycomeDefinitive hematopoietic stemEndothelial cellsHematopoietic fateMiR-223Mutant defectsGlycan biosynthesisN-glycosylationMetalloprotease ADAM10Intrinsic regulatorN-glycoproteinsHematopoietic stemProgenitor cellsHigh mannoseMicroRNA-223CellsKey determinantMannosyltransferaseMutantsLineagesBiosynthesis
2016
N-glycosylation critically regulates function of oxalate transporter SLC26A6
Thomson RB, Thomson CL, Aronson PS. N-glycosylation critically regulates function of oxalate transporter SLC26A6. American Journal Of Physiology - Cell Physiology 2016, 311: c866-c873. PMID: 27681177, PMCID: PMC5206297, DOI: 10.1152/ajpcell.00171.2016.Peer-Reviewed Original ResearchConceptsPlasma membraneIntegral membrane proteinsCell surface deliverySLC26A6 functionTissue-specific differencesGlycosylation mutantsMembrane proteinsN-glycosylationSurface deliveryBiotinylation studiesOxalate transporterOxalate homeostasisSecond extracellular loopExtracellular loopIntact cellsEnzymatic deglycosylation studiesTransport activityEnzymatic deglycosylationFunctional studiesDeglycosylation studiesGlycosylationPutative second extracellular loopTransport functionFunctional significanceEssential role
2014
N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*
Hofherr A, Wagner C, Fedeles S, Somlo S, Köttgen M. N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*. Journal Of Biological Chemistry 2014, 289: 14854-14867. PMID: 24719335, PMCID: PMC4031537, DOI: 10.1074/jbc.m114.562264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsparagineBinding SitesBlotting, WesternCell LineCells, CulturedGlucosidasesGlycosylationHEK293 CellsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMass SpectrometryMiceMice, KnockoutMicroscopy, FluorescenceMutationPolycystic Kidney, Autosomal DominantProtein Serine-Threonine KinasesProteolysisPyruvate Dehydrogenase Acetyl-Transferring KinaseConceptsGlucosidase IINon-catalytic β-subunitsProtein expressionFirst extracellular loopAutosomal dominant polycystic liver diseaseEfficient biogenesisGenetic interactionsMembrane proteinsBiochemical approachesN-glycosylationGenetic approachesTRPP2Glycosylation sitesBiological roleLysosomal degradationΒ-subunitChemical inhibitionBiogenesisExtracellular loopNonselective cation channelsIon channelsBiological importanceGlycosylationCation channelsProtein levels
2012
NogoB receptor is essential for extraembryonic vascular development and protein glycosylation
Park E, Sessa W. NogoB receptor is essential for extraembryonic vascular development and protein glycosylation. The FASEB Journal 2012, 26: 607.5-607.5. DOI: 10.1096/fasebj.26.1_supplement.607.5.Peer-Reviewed Original ResearchExtraembryonic vascular developmentDehydrodolichyl diphosphate synthaseProtein glycosylationPeri-implantation embryonic lethalityVascular developmentMutant yolk sacsProtein N-glycosylationYolk sacCKO embryosMutant embryosUseful model systemNon-functional formEmbryonic lethalityDiphosphate synthaseExtraembryonic tissuesN-glycosylationProtein stabilityEndothelial cellsConditional knockout miceDevelopment defectsTube formationMutantsCKO mouse modelModel systemEmbyronic developmentSpecific N‐glycans on SynCAM Ig proteins regulate synaptic adhesion and synapse development
Biederer T. Specific N‐glycans on SynCAM Ig proteins regulate synaptic adhesion and synapse development. The FASEB Journal 2012, 26: 232.2-232.2. DOI: 10.1096/fasebj.26.1_supplement.232.2.Peer-Reviewed Original ResearchTrans-synaptic interactionsSynapse developmentN-glycansSite-specific N-glycosylationSpecialized cell junctionsSpecific N-glycansProtein complexesFirst Ig domainN-glycosylationBinding interfaceSynaptic adhesionIg domainsFunctional analysisSynCAM 1Cell junctionsIg1 domainImmunoglobulin proteinNovel mechanismIg proteinGlycosylationProteinAdhesive interactionsSynCAMSynaptic cleftExcitatory synapses
2010
N-Glycosylation at the SynCAM (Synaptic Cell Adhesion Molecule) Immunoglobulin Interface Modulates Synaptic Adhesion*
Fogel AI, Li Y, Giza J, Wang Q, Lam TT, Modis Y, Biederer T. N-Glycosylation at the SynCAM (Synaptic Cell Adhesion Molecule) Immunoglobulin Interface Modulates Synaptic Adhesion*. Journal Of Biological Chemistry 2010, 285: 34864-34874. PMID: 20739279, PMCID: PMC2966101, DOI: 10.1074/jbc.m110.120865.Peer-Reviewed Original ResearchConceptsN-glycosylationTrans-synaptic interactionsN-glycansSite-specific N-glycansSynaptic cell adhesion molecule 1Site-specific N-glycosylationTrans-synaptic adhesionPost-translational modificationsSelect adhesion moleculesMutational studiesSynaptic adhesionGlycosylation sitesHeterophilic interactionsIg1 domainSynapse inductionPostsynaptic membraneAdhesion moleculesNeurobiological questionsSynaptic cleftStructural modelingPresynaptic terminalsDifferential mannerSialic acidCell adhesion molecule-1AdhesionMolecular characterization of the cis-prenyltransferase of Giardia lamblia
Grabińska K, Cui J, Chatterjee A, Guan Z, Raetz C, Robbins P, Samuelson J. Molecular characterization of the cis-prenyltransferase of Giardia lamblia. Glycobiology 2010, 20: 824-832. PMID: 20308470, PMCID: PMC2900897, DOI: 10.1093/glycob/cwq036.Peer-Reviewed Original ResearchConceptsIsoprene unitsDouble deletion mutantGPI anchor synthesisMost eukaryotesHigher eukaryotesAnchor synthesisN-glycosylationGlycosylphosphatidylinositol (GPI) anchorCis-prenyltransferaseKinase activityPolyprenyl pyrophosphateBacterial enzymesDolichol kinase activityDolichol kinaseMolecular characterizationImportant enzymeN-glycansEukaryotesProtistsPolyprenol lipidsNormal growthPyrophosphate linkageEnzymeGiardia lambliaDolichol
2009
The YTA7 gene is involved in the regulation of the isoprenoid pathway in the yeast Saccharomyces cerevisiae
Kuranda K, Grabinska K, Berges T, Karst F, Leberre V, Sokol S, François J, Palamarczyk G. The YTA7 gene is involved in the regulation of the isoprenoid pathway in the yeast Saccharomyces cerevisiae. FEMS Yeast Research 2009, 9: 381-390. PMID: 19416104, DOI: 10.1111/j.1567-1364.2009.00485.x.Peer-Reviewed Original ResearchConceptsIsoprenoid pathwayFPP synthaseTwo-hybrid screenMembrane-associated proteinsBiosynthesis of hemeIsoprenoid biosynthesisProtein partnersPresence of lovastatinYeast SaccharomycesN-glycosylationSterol biosynthesisSqualene synthaseCis-prenyltransferaseEndoplasmic reticulumIsoprenoid compoundsZaragozic acidsBiosynthesisCellular levelGenesEnzymatic activityExpression levelsSaccharomycesPathwaySynthaseRegulation
1998
Melanoma × Macrophage Fusion Hybrids Acquire Increased Melanogenesis and Metastatic Potential: Altered N‐Glycosylation as an Underlying Mechanism
SODI S, CHAKRABORTY A, PLATT J, KOLESNIKOVA N, ROSEMBLAT S, KEH‐YEN A, BOLOGNIA J, RACHKOVSKY M, ORLOW S, PAWELEK J. Melanoma × Macrophage Fusion Hybrids Acquire Increased Melanogenesis and Metastatic Potential: Altered N‐Glycosylation as an Underlying Mechanism. Pigment Cell & Melanoma Research 1998, 11: 299-309. PMID: 9877101, DOI: 10.1111/j.1600-0749.1998.tb00739.x.Peer-Reviewed Original ResearchConceptsN-glycosylationLAMP-1Parental cellsN-glycosylation inhibitorMelanoma cellsCloudman S91 cellsMetastatic potentialImportant regulatory pathwayAltered N-glycosylationMajority of hybridsParental melanoma cellsCloudman S91 melanoma cellsRegulatory pathwaysMelanosomal proteinsCloudman melanoma cellsMelanotic phenotypeSame proteinS91 melanoma cellsIncreased glycosylationPigmentary systemCell lysatesS91 cellsUnderlying mechanismCloudman cellsGel electrophoresis
1993
Molecular analyses of a tyrosinase-negative albino family.
Park K, Chintamaneni C, Halaban R, Witkop C, Kwon B. Molecular analyses of a tyrosinase-negative albino family. American Journal Of Human Genetics 1993, 52: 406-13. PMID: 8430701, PMCID: PMC1682201.Peer-Reviewed Original ResearchMeSH KeywordsAlbinism, OculocutaneousBase SequenceBlotting, NorthernBlotting, SouthernChildDNA Mutational AnalysisElectrophoresis, Polyacrylamide GelFemaleFrameshift MutationGene LibraryGlycosylationHumansMaleMelanocytesMolecular Sequence DataMonophenol MonooxygenaseMutationPedigreePoint MutationPolymerase Chain ReactionPrecipitin TestsSequence DeletionConceptsAmino acid changesAcid changesPutative amino acid changesPremature termination signalTwo-nucleotide deletionSingle base substitutionTermination signalGel electrophoretic analysisN-glycosylationCDNA libraryBase pair deletionCodon 355Genomic DNAHomologous allelesNucleotide substitutionsSequence analysisMolecular analysisMissense mutationsTwo-base deletionExon 1Electrophoretic analysisCodon 226Exon 3AllelesTyrosinase-negative oculocutaneous albinism
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