2013
Polycystin-1 cleavage and the regulation of transcriptional pathways
Merrick D, Bertuccio CA, Chapin HC, Lal M, Chauvet V, Caplan MJ. Polycystin-1 cleavage and the regulation of transcriptional pathways. Pediatric Nephrology 2013, 29: 505-511. PMID: 23824180, PMCID: PMC3844055, DOI: 10.1007/s00467-013-2548-y.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseFluid-filled renal cystsPolycystin-2Transcriptional pathwaysPolycystin-1Primary ciliaProtein productsPhysiological functionsCommon genetic causeParent proteinProteolytic cleavageCleavage fragmentsGenetic causeGenesEnd-stage renal diseaseDominant polycystic kidney diseasePolycystic kidney diseaseBiological activityPathwayRenal diseaseKidney diseaseCleavageRenal parenchymaFragmentsRenal cystsPolycystin-1C terminus cleavage and its relation with polycystin-2, two proteins involved in polycystic kidney disease.
Bertuccio CA, Caplan MJ. Polycystin-1C terminus cleavage and its relation with polycystin-2, two proteins involved in polycystic kidney disease. Medicina 2013, 73: 155-62. PMID: 23570767.Peer-Reviewed Original ResearchConceptsPolycystin-1Polycystin-2Autosomal dominant polycystic kidney diseaseTerminal cytoplasmic tailProtein sortingNormal tubulogenesisPolycystic kidney diseaseProtein functionCytoplasmic tailTerminal tailCommon genetic causeCystogenic processExtracellular matrixDifferentiation mechanismsCellular proliferationGenetic causeMultiple cleavagesDominant polycystic kidney diseasePathwayHigh proliferative rateCleavageProliferative rateSecretory characteristicsGenesTubulogenesis
2011
Interactions between β-Catenin and the HSlo Potassium Channel Regulates HSlo Surface Expression
Bian S, Bai JP, Chapin H, Le Moellic C, Dong H, Caplan M, Sigworth FJ, Navaratnam DS. Interactions between β-Catenin and the HSlo Potassium Channel Regulates HSlo Surface Expression. PLOS ONE 2011, 6: e28264. PMID: 22194818, PMCID: PMC3237428, DOI: 10.1371/journal.pone.0028264.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBeta CateninBinding SitesBiological AssayCell MembraneChickensGene Knockdown TechniquesHair Cells, AuditoryHEK293 CellsHumansImmunoprecipitationIntercellular JunctionsKineticsLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsModels, MolecularMolecular Sequence DataMutant ProteinsMutationPhosphorylationProtein BindingProtein TransportRNA, Small InterferingSequence DeletionTransfectionWnt Signaling PathwayConceptsΒ-cateninS10 regionHEK cellsSurface expressionCell biology toolsPotassium channel alpha subunitΒ-catenin interactionDownregulation of WntCytoskeleton frameworkChannel alpha subunitChicken hair cellsPhosphorylation sitesDeletion mutantsBiology toolsΒ-catenin-dependent canonical WntAlpha subunitCanonical WntMultiple binding sitesNumber of diseasesStable bindingWntPhysiological significanceBinding sitesReduced expressionHair cellsPolycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases
Choi YH, Suzuki A, Hajarnis S, Ma Z, Chapin HC, Caplan MJ, Pontoglio M, Somlo S, Igarashi P. Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 10679-10684. PMID: 21670265, PMCID: PMC3127890, DOI: 10.1073/pnas.1016214108.Peer-Reviewed Original ResearchConceptsPolycystin-2Primary ciliaA-kinase anchoring protein 150Dysregulation of cAMPTranscription factor hepatocyte nuclear factor-1βCystic kidney diseasePolycystic kidney diseaseCAMP levelsAKAP complexesRenal primary ciliaRenal epithelial cellsProtein complexesSensory organellesHuman polycystic kidney diseaseC-terminusProtein 150Hepatocyte nuclear factor-1βCalcium channel activityCell surfaceChannel activityCiliaKidney cystsKidney cellsDifferent gene mutationsEpithelial cellsRenal Cystic Disease Proteins Play Critical Roles in the Organization of the Olfactory Epithelium
Pluznick JL, Rodriguez-Gil DJ, Hull M, Mistry K, Gattone V, Johnson CA, Weatherbee S, Greer CA, Caplan MJ. Renal Cystic Disease Proteins Play Critical Roles in the Organization of the Olfactory Epithelium. PLOS ONE 2011, 6: e19694. PMID: 21614130, PMCID: PMC3094399, DOI: 10.1371/journal.pone.0019694.Peer-Reviewed Original ResearchConceptsRenal cystic diseaseOlfactory sensory neuronsOlfactory epitheliumCystic diseaseMutant animalsMature olfactory sensory neuronsMurine olfactory epitheliumDendritic knobsOlfactory adenylate cyclaseReceptor expressionSensory neuronsTransduction cascadeLaminar organizationDisease proteinMicrotubule architectureMKS1Syndrome 1Reduced expressionAdenylate cyclaseRT-PCRMKS3DiseaseProteinPhysiological activityObvious alterations
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 channelsAssociation with β-COP Regulates the Trafficking of the Newly Synthesized Na,K-ATPase*
Morton MJ, Farr GA, Hull M, Capendeguy O, Horisberger JD, Caplan MJ. Association with β-COP Regulates the Trafficking of the Newly Synthesized Na,K-ATPase*. Journal Of Biological Chemistry 2010, 285: 33737-33746. PMID: 20801885, PMCID: PMC2962472, DOI: 10.1074/jbc.m110.141119.Peer-Reviewed Original ResearchConceptsK-ATPase αK-ATPase β-subunitΒ-COPΒ-subunitΑ-subunitPlasma membraneEndoplasmic reticulumK-ATPase α-subunitMutant α-subunitsIon-transporting ATPasePlasma membrane expressionK-ATPasePulse-chase experimentsPartner proteinsNovel labeling techniqueCoat proteinDibasic motifCell surfaceMembrane expressionObligate intermediateΒ subunit expressionProteinReticulum
2009
Partial Correction of Cystic Fibrosis Defects with PLGA Nanoparticles Encapsulating Curcumin
Cartiera MS, Ferreira EC, Caputo C, Egan ME, Caplan MJ, Saltzman WM. Partial Correction of Cystic Fibrosis Defects with PLGA Nanoparticles Encapsulating Curcumin. Molecular Pharmaceutics 2009, 7: 86-93. PMID: 19886674, PMCID: PMC2815009, DOI: 10.1021/mp900138a.Peer-Reviewed Original ResearchAdministration, OralAnimalsBiological AvailabilityBiological Transport, ActiveCurcuminCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEnzyme InhibitorsHumansLactic AcidMiceMice, Inbred C57BLMice, Inbred CFTRMicroscopy, Electron, ScanningMutationNanoparticlesPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerSarcoplasmic Reticulum Calcium-Transporting ATPases
2006
CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney
Lu M, Leng Q, Egan ME, Caplan MJ, Boulpaep EL, Giebisch GH, Hebert SC. CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. Journal Of Clinical Investigation 2006, 116: 797-807. PMID: 16470247, PMCID: PMC1361349, DOI: 10.1172/jci26961.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCurcuminCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorHydrogen-Ion ConcentrationKidneyMiceMice, Inbred C57BLMice, Inbred CFTRMice, TransgenicMutationOocytesPatch-Clamp TechniquesPotassium Channels, Inwardly RectifyingXenopus laevisConceptsFunctional switchCystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channelATP sensitivityEffects of CFTRThick ascending limbPotential physiological rolePKA activityRenal K channelsCystic fibrosisPhysiological roleSecretory channelsK channelsRenal tubule epithelial cellsApical membraneCFTRDeltaF508 mutationDistal nephron segmentsCl- channelsK homeostasisTubule epithelial cellsEpithelial cellsTAL cellsPotassium channelsK handlingGlibenclamide sensitivity
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
Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects
Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glöckner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ. Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects. Science 2004, 304: 600-602. PMID: 15105504, DOI: 10.1126/science.1093941.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalnexinCell LineCell MembraneCricetinaeCurcuminCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorElectrolytesEndoplasmic ReticulumGene TargetingGlycosylationHumansIntestinal MucosaIntestinal ObstructionIsoproterenolMembrane PotentialsMiceMice, KnockoutMutationNasal MucosaPolyethylene GlycolsProtein FoldingRectumTransfectionConceptsCystic fibrosis transmembrane conductance regulatorCFTR proteinDeltaF508 cystic fibrosis transmembrane conductance regulatorDeltaF508 CFTR proteinFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorBaby hamster kidney cellsPlasma membraneComplete knockoutConductance regulatorHamster kidney cellsEndoplasmic reticulumCystic fibrosis defectCFTR geneKidney cellsCFTR miceGenesProteinMutationsCommon mutationsHomozygous expressionCurcumin treatmentFunctional appearanceWeight basisRegulator
2003
Polycystin-1 Distribution Is Modulated by Polycystin-2 Expression in Mammalian Cells*
Grimm DH, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, Avner ED, Sweeney W, Somlo S, Caplan MJ. Polycystin-1 Distribution Is Modulated by Polycystin-2 Expression in Mammalian Cells*. Journal Of Biological Chemistry 2003, 278: 36786-36793. PMID: 12840011, DOI: 10.1074/jbc.m306536200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell LineCell MembraneCells, CulturedCOS CellsDNA, ComplementaryEndoplasmic ReticulumGene Expression RegulationMembrane ProteinsMiceMice, TransgenicMicroscopy, FluorescenceModels, BiologicalMutationPrecipitin TestsProtein BindingProtein BiosynthesisProteinsRecombinant Fusion ProteinsRNA, MessengerTransfectionTRPP Cation ChannelsConceptsPolycystin-1Polycystin-2Mammalian cellsLevel of expressionPolycystin-2 expressionEndoplasmic reticulumCell surfaceCOS-7 cellsNull cell lineRelative expression levelsSubcellular localizationFusion proteinGradient of expressionExpression levelsProteinCell linesPolycystinsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseDivergent patternsExpressionPolycystic kidney diseaseReticulumCellsLocalization
2002
THE AQUAPORIN-2 WATER CHANNEL IN AUTOSOMAL DOMINANT PRIMARY NOCTURNAL ENURESIS
DEEN PM, DAHL N, CAPLAN MJ. THE AQUAPORIN-2 WATER CHANNEL IN AUTOSOMAL DOMINANT PRIMARY NOCTURNAL ENURESIS. Journal Of Urology 2002, 167: 1447-1450. PMID: 11832768, DOI: 10.1016/s0022-5347(05)65341-4.Peer-Reviewed Original Research
2000
Residues of the Fourth Transmembrane Segments of the Na,K-ATPase and the Gastric H,K-ATPase Contribute to Cation Selectivity*
Mense M, Dunbar L, Blostein R, Caplan M. Residues of the Fourth Transmembrane Segments of the Na,K-ATPase and the Gastric H,K-ATPase Contribute to Cation Selectivity*. Journal Of Biological Chemistry 2000, 275: 1749-1756. PMID: 10636871, DOI: 10.1074/jbc.275.3.1749.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid SequenceAnimalsCationsElectrophysiologyH(+)-K(+)-Exchanging ATPaseHydrogen-Ion ConcentrationInhibitory Concentration 50KineticsMolecular Sequence DataMutationOuabainPotassiumRecombinant Fusion ProteinsSequence Homology, Amino AcidSodiumSodium-Potassium-Exchanging ATPaseStomachVanadatesXenopus laevisConceptsFourth transmembrane segmentTransmembrane segmentsATPase assaysK-ATPaseHelical wheel analysisTwo-electrode voltage-clamp experimentsCation selectivityProtein chimerasXenopus laevis oocytesVanadate sensitivityWild-type NaGastric HK-ATPasesXenopus oocytesLaevis oocytesATPase activityAbsence of sodiumResiduesTM4K counterpartsControl constructsOocytesConformational equilibriumAssaysImportant role
1998
Conformational alterations resulting from mutations in cytoplasmic domains of the alpha subunit of the Na,K-ATPase.
Blostein R, Daly SE, Boxenbaum N, Lane LK, Arguello JM, Lingrel JB, Karlish SJ, Caplan MJ, Dunbar L. Conformational alterations resulting from mutations in cytoplasmic domains of the alpha subunit of the Na,K-ATPase. Acta Physiologica Scandinavica. Supplementum 1998, 643: 275-81. PMID: 9789570.Peer-Reviewed Original ResearchConceptsM2-M3 loopCytoplasmic domainCytoplasmic loopK-ATPaseN-terminusStructure/function analysisTransmembrane segment M2Amino-terminal halfMajor cytoplasmic loopFifth transmembrane segmentFirst cytoplasmic loopCatalytic phosphorylation siteMajor conformational statesLow catalytic turnoverPutative cationCytoplasmic mutantsTransmembrane segmentsPhosphorylation sitesTransmembrane domainAlpha 1 subunitSegment M2Cytoplasmic regionApparent affinityAmino terminusTerminal half
1995
Developmental regulation of membrane protein sorting in Drosophila embryos
Shiel MJ, Caplan MJ. Developmental regulation of membrane protein sorting in Drosophila embryos. American Journal Of Physiology 1995, 269: c207-c216. PMID: 7631747, DOI: 10.1152/ajpcell.1995.269.1.c207.Peer-Reviewed Original ResearchConceptsDrosophila embryosMembrane proteinsSurface ectodermTransgenic Drosophila embryosVesicular stomatitis virus G proteinDrosophila melanogaster embryosMammalian epithelial cellsPlacental alkaline phosphataseApical plasma membraneVirus G proteinBasolateral proteinsSorting pathwaysCytosolic portionDevelopmental regulationHuman placental alkaline phosphatasePlasma membraneBasolateral distributionChimeric constructsSubcellular distributionG proteinsApical membraneInternal epitheliumEmbryosProteinApical surface