2023
CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment
Muthana M, Du X, Liu M, Wang X, Wu W, Ai C, Su L, Zheng P, Liu Y. CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment. ELife 2023, 12: rp87281. PMID: 38127423, PMCID: PMC10735222, DOI: 10.7554/elife.87281.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsB-cell depletionB cellsT cellsSevere immune-related adverse eventsCTLA-4 antibody ipilimumabRegulatory T cell impairmentEffector memory T cellsAnti-TNF-alpha antibodyAnti-CTLA-4CTLA-4 deficiencyFoxP3<sup>+</sup> TregsCD8 T cellsT cell impairmentMemory T cellsRegulatory T cellsPeripheral B cellsB cell lossReduced peripheral B cellsSeveral autoimmune diseasesKnock-in miceAntibody-drug conjugatesAntibody ipilimumabCombination immunotherapyAutoimmune cytopeniasHeparin is essential for optimal cell signaling by FGF21 and for regulation of βKlotho cellular stability
An S, Mohanty J, Tome F, Suzuki Y, Lax I, Schlessinger J. Heparin is essential for optimal cell signaling by FGF21 and for regulation of βKlotho cellular stability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2219128120. PMID: 36745784, PMCID: PMC9962926, DOI: 10.1073/pnas.2219128120.Peer-Reviewed Original ResearchConceptsHeparan sulfate proteoglycanCellular stabilityCell membraneSingle-molecule fluorescenceProtein kinase responsesChinese hamster ovary cellsFGF moleculesHamster ovary cellsFactor bindsReceptor assemblyReceptor dimerizationGrowth factor bindsHigh-affinity bindingFGF1 stimulationKinase responseCHO cellsOvary cellsSulfate proteoglycanIntracellular CaKlotho proteinFGFR1cPotential roleRegulationΒKlothoCellsExcluding Digenic Inheritance of PGAP2 and PGAP3 Variants in Mabry Syndrome (OMIM 239300) Patient: Phenotypic Spectrum Associated with PGAP2 Gene Variants in Hyperphosphatasia with Mental Retardation Syndrome-3 (HPMRS3)
Thompson M, Li X, Spencer-Manzon M, Andrade D, Murakami Y, Kinoshita T, Carpenter T. Excluding Digenic Inheritance of PGAP2 and PGAP3 Variants in Mabry Syndrome (OMIM 239300) Patient: Phenotypic Spectrum Associated with PGAP2 Gene Variants in Hyperphosphatasia with Mental Retardation Syndrome-3 (HPMRS3). Genes 2023, 14: 359. PMID: 36833286, PMCID: PMC9957281, DOI: 10.3390/genes14020359.Peer-Reviewed Original ResearchConceptsDigenic inheritanceDeficient CHO cell lineCell linesGPI deficiency disordersDeficient cell linesCHO cell linesBiosynthesis genesGPI attachmentMabry syndromeProtein geneStrong promoterCHO cellsUnknown significanceGenesInheritanceGene variantsAutosomal recessive inheritanceHomozygous variantNeurologic deficitsVariantsCase reportRecessive inheritanceSyndrome patientsCD55 expressionPGAP2
2022
Single particle cryo-EM structure of the outer hair cell motor protein prestin
Butan C, Song Q, Bai JP, Tan WJT, Navaratnam D, Santos-Sacchi J. Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature Communications 2022, 13: 290. PMID: 35022426, PMCID: PMC8755724, DOI: 10.1038/s41467-021-27915-z.Peer-Reviewed Original ResearchConceptsTransmembrane domainProtein prestinSingle-particle cryo-EM structuresAnti-sigma factor antagonist domainOuter hair cell motor protein prestinCryo-EM structureCryo-electron microscopyMotor protein prestinSLC26 family membersSulfate transportersTransmembrane segmentsPrestin functionÅ resolutionPrestinOHC electromotilityOpen stateCochlear amplificationPutative mechanismsFamily membersDomainRepeatsSLC26A9TransportersMutationsElectromotility
2021
ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody
Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray N, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6: e145875. PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.Peer-Reviewed Original ResearchConceptsBlood-brain barrierAnti-DNA autoantibodiesBrain tumorsBreast cancer brain metastasesBlood-brain barrier transportBrain tumor immunotherapyCancer brain metastasesBrain endothelial cellsEndothelial cell penetrationCNS lupusNeurotoxic autoantibodiesBrain metastasesTumor immunotherapyBarrier transportAntibody-based approachesCNS penetrationAutoantibodiesEfficacy studiesOrthotopic glioblastomaEndothelial cellsTumorsCancer cellsNucleoside fluxesActionable mechanismsKey transportersA KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation
Zhang Y, Ali SR, Nabbout R, Barcia G, Kaczmarek LK. A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation. Journal Of Neurophysiology 2021, 126: 532-539. PMID: 34232791, PMCID: PMC8409950, DOI: 10.1152/jn.00257.2021.Peer-Reviewed Original ResearchConceptsFunctional channelsProtein kinase C.Serious human diseasesPotassium channelsWild-type channelsEpilepsy of infancyChannel modulationTerminal domainIon channel mutationsPKC phosphorylationC-terminusNormal neuronal functionChannel proteinsKv3.1 potassium channelRegulatory sitesKinase C.Human diseasesChannel functionPhosphorylationIon channelsMutationsNovo variantsChannel mutationsBiophysical propertiesNeuronal functionPresynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles
Wu XS, Subramanian S, Zhang Y, Shi B, Xia J, Li T, Guo X, El-Hassar L, Szigeti-Buck K, Henao-Mejia J, Flavell RA, Horvath TL, Jonas EA, Kaczmarek LK, Wu LG. Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles. Neuron 2021, 109: 938-946.e5. PMID: 33508244, PMCID: PMC7979485, DOI: 10.1016/j.neuron.2021.01.006.Peer-Reviewed Original ResearchConceptsSlow endocytosisVesicle mobilizationF-actin cytoskeletonChannel mutationsPotassium channelsKv3.3 proteinsInhibits endocytosisRapid endocytosisNovel functionF-actinEndocytosisCrucial functionSynaptic vesiclesFamily channelsSynaptic transmissionDiscovery decadesMembrane potentialNeurotransmitter releaseDiverse neurological disordersIon conductanceMutationsReleasable poolMouse nerve terminalsPotassium channel mutationsPathological effects
2020
Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding
Kadry YA, Maisuria EM, Huet-Calderwood C, Calderwood DA. Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding. Journal Of Biological Chemistry 2020, 295: 11161-11173. PMID: 32546480, PMCID: PMC7415974, DOI: 10.1074/jbc.ra120.013618.Peer-Reviewed Original ResearchConceptsKindlin-3Kindlin-2Focal adhesionsIntegrin cytoplasmic domainTransmembrane adhesion receptorsComparative sequence analysisLive-cell imagingAbility of cellsCytoplasmic domainF3 subdomainsMammalian cellsCytoplasmic componentsExtracellular environmentAdhesion receptorsKindlinSequence analysisIntegrin familySelf-associationIntegrin bindingPhysiological importanceMolecular levelPoint mutationsProteinCellsAdhesionCX3CL1 homo-oligomerization drives cell-to-cell adherence
Ostuni M, Hermand P, Saindoy E, Guillou N, Guellec J, Coens A, Hattab C, Desuzinges-Mandon E, Jawhari A, Iatmanen-Harbi S, Lequin O, Fuchs P, Lacapere J, Combadière C, Pincet F, Deterre P. CX3CL1 homo-oligomerization drives cell-to-cell adherence. Scientific Reports 2020, 10: 9069. PMID: 32494000, PMCID: PMC7271195, DOI: 10.1038/s41598-020-65988-w.Peer-Reviewed Original ResearchConceptsNumerous adhesion moleculesPhotobleaching assaysNative electrophoresisAdhesive potencyTransmembrane peptidesLipid environmentKey immune processesAdhesive functionFluorescence recoveryFunctional roleDomain peptideFluorescence kineticsOligomerizationCellular adherenceMolecular modelingAdhesion moleculesCell adherenceTransmembrane chemokineImmune processesCompact bundlePeptidesBlood leukocytesClustersElectrophoresisCX3CL1Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes.
Jarlhelt I, Pilely K, Clausen J, Skjoedt M, Bayarri-Olmos R, Garred P. Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes. The Journal Of Immunology 2020, 204: 1919-1928. PMID: 32094208, DOI: 10.4049/jimmunol.1900694.Peer-Reviewed Original ResearchConceptsProtein complexesHeteromeric protein complexesNovel protein complexChinese hamster ovary cellsHamster ovary cellsPattern recognition moleculesHeterocomplexWestern blot analysisInnate immune systemBiological relevanceOvary cellsBlot analysisRecognition moleculesFicolin-2Soluble pattern recognition moleculesFicolin-3Lectin pathwayComplexesImmune systemCoimmunoprecipitationComplement systemMoleculesC1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule That Recruits Collectin-11 from the Complement System to Ligands.
Kirketerp-Møller N, Bayarri-Olmos R, Krogfelt K, Garred P. C1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule That Recruits Collectin-11 from the Complement System to Ligands. The Journal Of Immunology 2020, 204: 1598-1606. PMID: 32041782, DOI: 10.4049/jimmunol.1901316.Peer-Reviewed Original ResearchConceptsPattern recognition moleculesProtein 6Recognition moleculesLectin complement pathwayChinese hamster ovary cellsGram-negative bacteriaProtein familyHamster ovary cellsSpecific recruitmentPutative ligandCollectin-11Human lectinsOvary cellsC1q/TNF-related protein 6Innate immunityBacterial isolatesBindingPathwayEndocrine processesCTRP6Complement recognitionGlobular structureEndogenous ligandComplement pathwayEnzymeSerine phosphorylation of the small phosphoprotein ICAP1 inhibits its nuclear accumulation
Su VL, Simon B, Draheim KM, Calderwood DA. Serine phosphorylation of the small phosphoprotein ICAP1 inhibits its nuclear accumulation. Journal Of Biological Chemistry 2020, 295: 3269-3284. PMID: 32005669, PMCID: PMC7062153, DOI: 10.1074/jbc.ra119.009794.Peer-Reviewed Original ResearchConceptsIntegrin cytoplasmic domain-associated protein-1N-terminal regionNuclear accumulationP21-activated kinase 4Ser-10Nuclear roleSerine phosphorylationNuclear localizationPhosphorylation-mimicking substitutionsNuclear localization signalCell-cell junctionsSer-25Localization signalKRIT1 functionThreonine residuesAdaptor proteinKRIT1 lossSubcellular localizationNeurovascular dysplasiaBlood vessel integrityVascular developmentKinase 4Cultured cellsPhosphorylationProtein 1
2019
Mammalian TRP ion channels are insensitive to membrane stretch
Nikolaev YA, Cox CD, Ridone P, Rohde PR, Cordero-Morales JF, Vásquez V, Laver DR, Martinac B. Mammalian TRP ion channels are insensitive to membrane stretch. Journal Of Cell Science 2019, 132: jcs238360. PMID: 31722978, PMCID: PMC6918743, DOI: 10.1242/jcs.238360.Peer-Reviewed Original ResearchConceptsTRP channelsTouch-insensitive mutantsMembrane stretchIon channelsTRP ion channel familyIon channel familyTransient receptor potential (TRP) ion channelsTRP ion channelsMammalian subfamiliesMammalian membersPotential ion channelsArtificial bilayer systemInsensitive mutantsCytoplasmic tethersDownstream componentsMechanosensory processesSignaling cascadesChannel familyCellular componentsBlood pressure regulationCell membraneCerebrospinal fluid flowMechanical forcesStretch activationPressure regulationThe EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research 2019, 25: 6382-6391. PMID: 31182434, PMCID: PMC6825535, DOI: 10.1158/1078-0432.ccr-19-0780.Peer-Reviewed Original ResearchCalcium Phosphate-Mediated Transfection of Eukaryotic Cells with Plasmid DNAs.
Kumar P, Nagarajan A, Uchil PD. Calcium Phosphate-Mediated Transfection of Eukaryotic Cells with Plasmid DNAs. Cold Spring Harbor Protocols 2019, 2019: pdb.prot095430. PMID: 31575793, DOI: 10.1101/pdb.prot095430.Peer-Reviewed Original ResearchCalcium Phosphate-Mediated Transfection of Cells with High-Molecular-Weight Genomic DNA.
Kumar P, Nagarajan A, Uchil PD. Calcium Phosphate-Mediated Transfection of Cells with High-Molecular-Weight Genomic DNA. Cold Spring Harbor Protocols 2019, 2019: pdb.prot095448. PMID: 31575794, DOI: 10.1101/pdb.prot095448.Peer-Reviewed Original ResearchCombining MAP‐1:CD35 or MAP‐1:CD55 fusion proteins with pattern‐recognition molecules as novel targeted modulators of the complement cascade
Pérez‐Alós L, Bayarri‐Olmos R, Skjoedt M, Garred P. Combining MAP‐1:CD35 or MAP‐1:CD55 fusion proteins with pattern‐recognition molecules as novel targeted modulators of the complement cascade. The FASEB Journal 2019, 33: 12723-12734. PMID: 31469600, PMCID: PMC6902692, DOI: 10.1096/fj.201901643r.Peer-Reviewed Original ResearchConceptsMannose-binding lectinComplement cascadePattern recognition moleculesFeasible therapeutic optionLevels of C3Lectin pathwayEffective therapeutic approachTerminal effector functionsComplement activation assaysSites of inflammationComplement receptor 1Membrane-anchored regulatorTerminal complement complexTherapeutic optionsInflammatory pathologyLP activationTherapeutic approachesEffector functionsDecay-accelerating factorFicolin-3Receptor 1CD35Complement complexMAP-1Complement systemSite‐specific phosphorylation of villin remodels the actin cytoskeleton to regulate Sendai viral glycoprotein‐mediated membrane fusion
Chandra S, Kumar M, Sharma N, Sarkar D. Site‐specific phosphorylation of villin remodels the actin cytoskeleton to regulate Sendai viral glycoprotein‐mediated membrane fusion. FEBS Letters 2019, 593: 1927-1943. PMID: 31183850, DOI: 10.1002/1873-3468.13477.Peer-Reviewed Original ResearchConceptsMembrane fusionVirus-host cell membrane fusionKey phosphorylation sitesQuantitative mass spectrometrySite-specific phosphorylationCell membrane fusionChinese hamster ovary cellsActin cytoskeletonPhosphorylation sitesHamster ovary cellsC-SrcTyrosine phosphorylationDependent phosphorylationCellular factorsCell fusionPhosphorylationOvary cellsVillinCritical roleVillin expressionSendai virosomesMass spectrometryFusionImportant roleCytoskeletonEarly Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor
Alfajaro M, Cho E, Kim D, Kim J, Park J, Soliman M, Baek Y, Park C, Kang M, Park S, Cho K. Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor. Journal Of Virology 2019, 93: 10.1128/jvi.01773-18. PMID: 30463963, PMCID: PMC6364031, DOI: 10.1128/jvi.01773-18.Peer-Reviewed Original ResearchConceptsSevere acute gastroenteritisClaudin-1Acute gastroenteritisEntry factorsTight junctionsTJ proteinsLLC-PK cellsAdhesion molecule-1Common causative agentChinese hamster ovaryDisrupts tight junctionsIntestinal epithelial cellsTransepithelial electrical resistanceHisto-blood groupTJ protein occludinRole of TJsMolecule-1Functional coreceptorInfectionTerminal sialic acidAffordable drugsProtein occludinOccludinSpecific antibodiesEpithelial cells
2018
Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1)
Bayarri-Olmos R, Kirketerp-Moller N, Pérez-Alós L, Skjodt K, Skjoedt M, Garred P. Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1). Frontiers In Immunology 2018, 9: 2238. PMID: 30323815, PMCID: PMC6172411, DOI: 10.3389/fimmu.2018.02238.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntibodies, MonoclonalCHO CellsChromatography, GelCollectinsComplement C4CricetulusEnzyme-Linked Immunosorbent AssayFreezingHumansLectinsMannose-Binding Protein-Associated Serine ProteasesProtein BindingStatistics, NonparametricSystemic Inflammatory Response SyndromeZymosanConceptsPlasma levelsSystemic inflammatory response syndromeQuantitative ELISACL-11Immunoprecipitation of serumDisseminated intravascular coagulationInflammatory response syndromeMean plasma concentrationCollectin-11Pattern recognition moleculesIntravascular coagulationResponse syndromeIntensive careUrinary schistosomiasisHealthy controlsPlasma concentrationsClinical toolHost defenseSensitive ELISAMonoclonal antibodiesELISACongenital disorderSignificant decreaseLectin pathwayZymosan
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