2025
Suppression of Autosomal Dominant Polycystic Kidney Disease Influences Epithelial Cell Transcription Program
Rai V, Failli M, Fiusco M, Reyna-Neyra A, Onuchic L, di Bernardo D, Craft J, Caplan M. Suppression of Autosomal Dominant Polycystic Kidney Disease Influences Epithelial Cell Transcription Program. Physiology 2025, 40: 0966. DOI: 10.1152/physiol.2025.40.s1.0966.Peer-Reviewed Original ResearchC-terminal tailCystic phenotypeTranscriptional programsAutosomal dominant polycystic kidney diseaseScRNA-seqTranscriptional differencesAmino acid C-terminal tailAcidic C-terminal tailPolycystin-1 proteinCell transcriptional programDifferentiated cell stateEpithelial cellsSingle cell RNA sequencingDoxycycline-inducible mouse modelCell RNA sequencingNovel transcriptsLibrary preparationCell transcriptional profilingChromium technologyPKD1 geneBiological replicatesRNA velocityCDNA synthesisRNA sequencingTranscriptional profiles
2024
Identification of Early Transcriptional Markers of Autosomal Dominant Polycystic Kidney Disease Cystic Epithelial Cells
Rai V, Failli M, Fiusco M, Reyna-Neyra A, di Bernardo D, Craft J, Caplan M. Identification of Early Transcriptional Markers of Autosomal Dominant Polycystic Kidney Disease Cystic Epithelial Cells. Physiology 2024, 39: 1176. DOI: 10.1152/physiol.2024.39.s1.1176.Peer-Reviewed Original ResearchC-terminal tailAutosomal dominant polycystic kidney diseaseScRNA-seqPolycystin-1 C-terminal tailPolycystin-1 proteinEpithelial cellsSingle cell RNA sequencingTranscriptional signatureCell RNA sequencingLibrary preparationChromium technologyCystic epithelial cellsBiological replicatesPolycystin-1Amino acid portionTranscriptional programsCDNA synthesisRNA sequencingTranscriptional changesTranscriptional profilesCyst epithelial cellsExpression of multiple markersMonogenic diseasesDominant polycystic kidney diseaseProtein expression levelsNoncanonical interaction with microtubules via the N-terminal nonmotor domain is critical for the functions of a bidirectional kinesin
Singh S, Siegler N, Pandey H, Yanir N, Popov M, Goldstein-Levitin A, Sadan M, Debs G, Zarivach R, Frank G, Kass I, Sindelar C, Zalk R, Gheber L. Noncanonical interaction with microtubules via the N-terminal nonmotor domain is critical for the functions of a bidirectional kinesin. Science Advances 2024, 10: eadi1367. PMID: 38324691, PMCID: PMC10849588, DOI: 10.1126/sciadv.adi1367.Peer-Reviewed Original ResearchConceptsBidirectional motilityKinesin-5Plus-end-directed motilityKinesin-5 motorsCryo-EMC-terminal tailCryo-EM mapsPlus-end-directed kinesinCryo-electron microscopyDeletion mutantsNoncanonical interactionsIntracellular functionsCin8Cryo-electronMotor domainMotilityNonmotor domainsMutantsB-tubulinSingle-moleculeCell viabilityIn vivoIn vitroIn vitro experimentsLocal defects
2023
Abl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation
Duan D, Lyu W, Chai P, Ma S, Wu K, Wu C, Xiong Y, Sestan N, Zhang K, Koleske A. Abl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation. Current Biology 2023, 33: 4582-4598.e10. PMID: 37858340, PMCID: PMC10877310, DOI: 10.1016/j.cub.2023.09.018.Peer-Reviewed Original ResearchConceptsCOS-7 cellsMT nucleationMT latticeFamily kinasesTubulin recruitmentLiquid-liquid phase separationTubulin C-terminal tailsCryo-EM analysisC-terminal tailAbl family kinasesWild-type cellsC-terminal halfRescue frequencyGenetic experimentsNeuronal morphogenesisMicrotubule nucleationSplice isoformsMicrotubule dynamicsNocodazole treatmentMolecular mechanismsAxon guidanceCell migrationDamage sitesABL2MT assemblySpecies-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast
Sultana S, Abdullah M, Li J, Hochstrasser M, Kachroo A. Species-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast. Genetics 2023, 225: iyad117. PMID: 37364278, PMCID: PMC10471208, DOI: 10.1093/genetics/iyad117.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsYeast proteasomeLocal protein-protein interactionsSpecific protein-protein interactionsYeast proteasome subunitsVast evolutionary distancesC-terminal tailFull-length tailThousands of genesHigh-throughput pipelineYeast counterpartEvolutionary divergenceEvolutionary distanceAssembly intermediatesHuman genesProteasome subunitsComplementationProteasomeSubunitsYeastGenesDistinct interactionsCore assemblyHuman β3Β3 subunit
2022
Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry
Simon B, Lou HJ, Huet-Calderwood C, Shi G, Boggon TJ, Turk BE, Calderwood DA. Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry. Nature Communications 2022, 13: 749. PMID: 35136069, PMCID: PMC8826447, DOI: 10.1038/s41467-022-28427-0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceCatalytic DomainCell Cycle ProteinsConserved SequenceCrystallography, X-RayHistonesHumansMolecular ChaperonesMolecular Docking SimulationMolecular MimicryMutagenesisPeptide LibraryPhosphorylationProtein KinasesRecombinant ProteinsSubstrate SpecificityConceptsTousled-like kinaseDNA replication-coupled nucleosome assemblyNuclear serine-threonine kinaseReplication-coupled nucleosome assemblyHistone chaperone proteinsGlobular N-terminal domainProper cell divisionPhosphorylation site motifsSerine-threonine kinaseShort sequence motifsAsf1 histone chaperonesC-terminal tailN-terminal domainHistone chaperonesGenome maintenanceNucleosome assemblySequence motifsChaperone proteinsNon-catalytic interactionsCatalytic domainCell divisionSite motifN-terminusStringent selectivityCell growth
2019
Structures of a RAG-like transposase during cut-and-paste transposition
Liu C, Yang Y, Schatz DG. Structures of a RAG-like transposase during cut-and-paste transposition. Nature 2019, 575: 540-544. PMID: 31723264, PMCID: PMC6872938, DOI: 10.1038/s41586-019-1753-7.Peer-Reviewed Original ResearchConceptsCryo-electron microscopy structureC-terminal tailUnique structural elementsStrand transfer complexEukaryotic cutEvolutionary progenitorsMicroscopy structureRAG recombinasePaste transpositionApo enzymeSubstrate DNAHelicoverpa zeaConformational changesEarly stepsTransposaseAdaptive immune systemDNATarget siteTransposonTarget DNAPivotal roleActive siteEnzymeTransposition processEssential componentRegulation of MT dynamics via direct binding of an Abl family kinase
Hu Y, Lyu W, Lowery LA, Koleske AJ. Regulation of MT dynamics via direct binding of an Abl family kinase. Journal Of Cell Biology 2019, 218: 3986-3997. PMID: 31699690, PMCID: PMC6891085, DOI: 10.1083/jcb.201812144.Peer-Reviewed Original ResearchConceptsAbl family kinasesC-terminal halfFamily kinasesMT dynamicsMT growthTubulin C-terminal tailsC-terminal tailStable reexpressionEssential regulatorCell shapeBinds microtubulesMT polymerizationAbl kinaseGenetic studiesDirect bindingFunctional interactionKinaseMicrotubulesABL2ReexpressionMT behaviorBindingRegulatorProteinGrowth
2018
Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ
Merrick D, Mistry K, Wu J, Gresko N, Baggs JE, Hogenesch JB, Sun Z, Caplan MJ. Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ. Human Molecular Genetics 2018, 28: 16-30. PMID: 30215740, PMCID: PMC6298236, DOI: 10.1093/hmg/ddy322.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBone DevelopmentCell DifferentiationE1A-Associated p300 ProteinGene Expression RegulationGenes, RegulatorHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsKidneyModels, AnimalMorpholinosOsteoblastsOsteogenesisPolycystic Kidney, Autosomal DominantTrans-ActivatorsTranscription FactorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTRPP Cation ChannelsZebrafishZebrafish ProteinsConceptsC-terminal tailCurly tail phenotypePolycystin-1Tail phenotypeTranscriptional coactivator TAZMessenger RNARunx2 transcriptional activityBone developmentTranscription factor Runx2Co-regulatory proteinsPkd1 mutant miceEssential coactivatorTranscriptional pathwaysTranscriptional activityOsteoblast differentiationKey mechanistic linkTAZPhysiological functionsPKD1 geneMechanistic linkRunx2MorpholinoPhenotypeMutant miceAutosomal dominant polycystic kidney disease
2013
Tetraspanin protein CD9 interacts with metalloprotease CD10 and enhances its release via exosomes
Mazurov D, Barbashova L, Filatov A. Tetraspanin protein CD9 interacts with metalloprotease CD10 and enhances its release via exosomes. The FEBS Journal 2013, 280: 1200-1213. PMID: 23289620, DOI: 10.1111/febs.12110.Peer-Reviewed Original ResearchConceptsPeptidase activityPre-B cellsTetraspanin CD9Cytoplasmic C-terminal domainC-terminal domainTetraspanin protein CD9C-terminal tailSite-directed mutagenesisShort hairpin RNA knockdownTransmembrane domain 4CD9 expressionMaturation of pre-B cellsLevel of CD10 expressionExtracellular matrix microenvironmentTetraspanin webCD10-positive cellsLevels of CD10Molecular partnersIntracellular proteinsMigration of B cellsStable expressionTetraspaninDomain 4Associated with CD9CD10 expression
2010
Polycystin-1 Surface Localization Is Stimulated by Polycystin-2 and Cleavage at the G Protein-coupled Receptor Proteolytic Site
Chapin HC, Rajendran V, Caplan MJ. Polycystin-1 Surface Localization Is Stimulated by Polycystin-2 and Cleavage at the G Protein-coupled Receptor Proteolytic Site. Molecular Biology Of The Cell 2010, 21: 4338-4348. PMID: 20980620, PMCID: PMC3002387, DOI: 10.1091/mbc.e10-05-0407.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell MembraneCiliaFluorescent Antibody TechniqueHEK293 CellsHumansImmunoprecipitationKidneyLLC-PK1 CellsMutationPolycystic Kidney, Autosomal DominantProtein BindingProtein IsoformsProtein Processing, Post-TranslationalProtein Structure, TertiaryProtein TransportSwineTRPP Cation ChannelsConceptsG-protein-coupled receptor proteolytic siteGPS cleavagePC2 channel activitySurface deliveryChannel activityProteolytic siteSurface localizationPlasma membrane localizationC-terminal tailHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsPC2 mutationsKidney 293 cellsMembrane localizationSecretory pathwayMembrane proteinsBinding partnerTerminal tailPolycystin-2Effect of PC2Plasma membraneCiliary membraneTRP familyLLC-PK cellsCation channelsMAL/VIP17, a New Player in the Regulation of NKCC2 in the Kidney
Carmosino M, Rizzo F, Procino G, Basco D, Valenti G, Forbush B, Schaeren-Wiemers N, Caplan MJ, Svelto M. MAL/VIP17, a New Player in the Regulation of NKCC2 in the Kidney. Molecular Biology Of The Cell 2010, 21: 3985-3997. PMID: 20861303, PMCID: PMC2982131, DOI: 10.1091/mbc.e10-05-0456.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell LineEndocytosisEpithelial CellsHumansImmunoprecipitationKidneyLLC-PK1 CellsMembrane Transport ProteinsMiceMice, TransgenicMyelin and Lymphocyte-Associated Proteolipid ProteinsMyelin ProteinsPhosphorylationProtein BindingProteolipidsRatsRats, Inbred WKYRNA InterferenceSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 1SwineConceptsRegulation of NKCC2Apical membraneMajor salt transport pathwayC-terminal tailCell surface retentionApical sortingPorcine kidney cellsCotransporter phosphorylationTransgenic mice resultsNephron structuresRegulated absorptionImportant roleNew playersKidney cellsSurface expressionMice resultsSurface retentionTransport pathwaysNKCC2MembraneRegulationLymphocyte-associated proteinCyst formationRat kidney medullaColocalizeA Comprehensive Model of the Spectrin Divalent Tetramer Binding Region Deduced Using Homology Modeling and Chemical Cross-linking of a Mini-spectrin [S] *
Li D, Harper SL, Tang HY, Maksimova Y, Gallagher PG, Speicher DW. A Comprehensive Model of the Spectrin Divalent Tetramer Binding Region Deduced Using Homology Modeling and Chemical Cross-linking of a Mini-spectrin [S] *. Journal Of Biological Chemistry 2010, 285: 29535-29545. PMID: 20610390, PMCID: PMC2937985, DOI: 10.1074/jbc.m110.145573.Peer-Reviewed Original ResearchConceptsHelix faceRed cell membrane stabilityHomology modelingNon-homologous tailsCell membrane stabilityC-terminal tailWild-type bindingMedium-resolution structureSubtle conformational changesTetramer complexSpectrin tetramer formationChemical Cross-LinkingMembrane skeletonRecombinant domainsTetramer formation
2009
Chapter 11 Detecting the Surface Localization and Cytoplasmic Cleavage of Membrane-Bound Proteins
Chapin HC, Rajendran V, Capasso A, Caplan MJ. Chapter 11 Detecting the Surface Localization and Cytoplasmic Cleavage of Membrane-Bound Proteins. Methods In Cell Biology 2009, 94: 223-239. PMID: 20362093, PMCID: PMC3063071, DOI: 10.1016/s0091-679x(08)94011-5.Peer-Reviewed Original ResearchConceptsC-terminal tailPolycystin-1Membrane-bound proteinsSubcellular localizationNuclear localizationPlasma membranePC1 proteinCytoplasmic cleavagePhysiological functionsSurface localizationFunctional roleSurface proteinsCell surfaceSurface populationsSpecific cleavageProteinImmunofluorescence protocolSoluble fragmentProtein expressionCell populationsImportant poolAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseCleavageComplete understandingRegulation of the epidermal growth factor receptor intracellular domain
Choi S, Lemmon M. Regulation of the epidermal growth factor receptor intracellular domain. The FASEB Journal 2009, 23: 883.2-883.2. DOI: 10.1096/fasebj.23.1_supplement.883.2.Peer-Reviewed Original ResearchC-terminal tailTyrosine kinase domainIntracellular domainJuxtamembrane regionJM regionEGFR intracellular domainEpidermal growth factor receptorC-tailEGFR extracellular regionC-tail regionReceptor intracellular domainEffects of mutationsReceptor tyrosine kinasesReceptor-receptor interactionsSmall-angle X-ray scatteringKinase assaysKinase domainGrowth factor receptorExtracellular regionReceptor dimerizationEGFR activationBaculovirus systemIntracellular dimerTyrosine kinaseDeletion mutations
2008
Polycystin-1 C-terminal tail associates with β-catenin and inhibits canonical Wnt signaling
Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ. Polycystin-1 C-terminal tail associates with β-catenin and inhibits canonical Wnt signaling. Human Molecular Genetics 2008, 17: 3105-3117. PMID: 18632682, PMCID: PMC2722884, DOI: 10.1093/hmg/ddn208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsbeta CateninBinding SitesCell LineCell NucleusCHO CellsCricetinaeCricetulusGene Expression ProfilingGene Expression RegulationHumansLigandsOligonucleotide Array Sequence AnalysisPeptide FragmentsPolycystic Kidney, Autosomal DominantRecombinant ProteinsSignal TransductionSystems BiologyTCF Transcription FactorsTransfectionTRPP Cation ChannelsWnt ProteinsConceptsC-terminal tailCanonical WntPolycystin-1Wnt-dependent signalingDNA microarray analysisDependent gene transcriptionN-terminal portionInhibits canonical WntTCF proteinsT-cell factorAutosomal dominant polycystic kidney disease (ADPKD) casesMotif presentGene transcriptionDevelopmental processesMicroarray analysisWntPKD1 geneΒ-cateninNovel mechanismRegulation of Polycystin‐1 C terminal cleavage by Polycystin‐2
Bertuccio C, Cai Y, Somlo S, Caplan M. Regulation of Polycystin‐1 C terminal cleavage by Polycystin‐2. The FASEB Journal 2008, 22: 942.9-942.9. DOI: 10.1096/fasebj.22.1_supplement.942.9.Peer-Reviewed Original Research
2005
The C-Terminal Tail of the Polycystin-1 Protein Interacts with the Na,K-ATPase α-Subunit
Zatti A, Chauvet V, Rajendran V, Kimura T, Pagel P, Caplan MJ. The C-Terminal Tail of the Polycystin-1 Protein Interacts with the Na,K-ATPase α-Subunit. Molecular Biology Of The Cell 2005, 16: 5087-5093. PMID: 16107561, PMCID: PMC1266409, DOI: 10.1091/mbc.e05-03-0200.Peer-Reviewed Original ResearchConceptsC-terminal tailPolycystin-1Cytoplasmic C-terminal tailK-ATPase α-subunitPolycystin-1 proteinK-ATPase activityRegulation of NaChinese hamster ovary cellsProtein interactsHamster ovary cellsProtein exhibitΑ-subunitFunctional studiesAmino acidsPKD1 geneOvary cellsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseasePolycystic kidney diseaseInteractsKinetic propertiesRegulationGenesTailProtein
2004
Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hieseberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. Journal Of Clinical Investigation 2004, 114: 1433-1443. PMID: 15545994, PMCID: PMC525739, DOI: 10.1172/jci21753.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell LineCell NucleusChlorocebus aethiopsCHO CellsCOS CellsCricetinaeCricetulusDogsEmbryo, MammalianEpithelial CellsKidney TubulesMembrane ProteinsMiceMice, TransgenicPolycystic Kidney, Autosomal DominantProteinsSequence DeletionSignal TransductionStress, MechanicalTranscription Factor AP-1TRPP Cation ChannelsConceptsC-terminal tailAutosomal dominant polycystic kidney diseaseCell-matrix interactionsCiliary signalingSecond genePolycystin-2Polycystin-1C-terminusNovel pathwayProteolytic cleavageNuclear translocationMechanical stimuliGenesDominant polycystic kidney diseasePolycystic kidney diseasePrecise mechanismCleavageTerminusSignalingTranslocationNucleusPathway
2002
The C-terminal Tails of HslU ATPase Act as a Molecular Switch for Activation of HslV Peptidase*
Seong IS, Kang MS, Choi MK, Lee JW, Koh OJ, Wang J, Eom SH, Chung CH. The C-terminal Tails of HslU ATPase Act as a Molecular Switch for Activation of HslV Peptidase*. Journal Of Biological Chemistry 2002, 277: 25976-25982. PMID: 12011053, DOI: 10.1074/jbc.m202793200.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid SequenceAmino Acid SubstitutionATP-Dependent ProteasesBinding SitesElectrophoresis, Polyacrylamide GelEndopeptidasesEnzyme ActivationHeat-Shock ProteinsModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedProtein ConformationSerine EndopeptidasesStructure-Activity RelationshipConceptsC-terminal tailHslV peptidaseHslVU complexC-terminusHexameric ringMolecular switchATP-dependent proteaseC-terminal 10 residuesAmino acidsProteolytic active sitesDodecamer consistingHslU hexamerHslU ATPaseTail peptideAxial poreATPase actsPolypeptide substratesSubstrate entryS proteasomeHslUCentral poreTerminusHslVPeptidaseCritical role
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