2006
Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif
Geng L, Okuhara D, Yu Z, Tian X, Cai Y, Shibazaki S, Somlo S. Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif. Journal Of Cell Science 2006, 119: 1383-1395. PMID: 16537653, DOI: 10.1242/jcs.02818.Peer-Reviewed Original Research
2005
Polycystin-2 Regulates Proliferation and Branching Morphogenesis in Kidney Epithelial Cells*
Grimm DH, Karihaloo A, Cai Y, Somlo S, Cantley LG, Caplan MJ. Polycystin-2 Regulates Proliferation and Branching Morphogenesis in Kidney Epithelial Cells*. Journal Of Biological Chemistry 2005, 281: 137-144. PMID: 16278216, DOI: 10.1074/jbc.m507845200.Peer-Reviewed Original ResearchConceptsPolycystin-2Kidney epithelial cellsPolycystin-1Cell proliferationRegulation of tubulogenesisWild-type proteinMultiple fluid-filled cystsAutosomal dominant polycystic kidney diseaseTubule formationEpithelial cellsExtracellular-related kinaseRegulatory machineryPolycystin proteinsBranching morphogenesisNegative regulatorRespective proteinsGenes PKD1Regulates ProliferationChannel mutantsMorphogenesisFluid-filled cystsCell growthProper growthChannel activityProtein
2004
Mutations in SEC63 cause autosomal dominant polycystic liver disease
Davila S, Furu L, Gharavi AG, Tian X, Onoe T, Qian Q, Li A, Cai Y, Kamath PS, King BF, Azurmendi PJ, Tahvanainen P, Kääriäinen H, Höckerstedt K, Devuyst O, Pirson Y, Martin RS, Lifton RP, Tahvanainen E, Torres VE, Somlo S. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nature Genetics 2004, 36: 575-577. PMID: 15133510, DOI: 10.1038/ng1357.Peer-Reviewed Original ResearchThe N-terminal Extracellular Domain Is Required for Polycystin-1-dependent Channel Activity*
Babich V, Zeng WZ, Yeh BI, Ibraghimov-Beskrovnaya O, Cai Y, Somlo S, Huang CL. The N-terminal Extracellular Domain Is Required for Polycystin-1-dependent Channel Activity*. Journal Of Biological Chemistry 2004, 279: 25582-25589. PMID: 15060061, DOI: 10.1074/jbc.m402829200.Peer-Reviewed Original ResearchDeficiency of polycystin‐2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells
Aguiari G, Banzi M, Gessi S, Cai Y, Zeggio E, Manzati E, Piva R, Lambertini E, Ferrari L, Peters DJ, Lanza F, Harris PC, Borea PA, Somlo S, del Senno L. Deficiency of polycystin‐2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells. The FASEB Journal 2004, 18: 884-886. PMID: 15001556, DOI: 10.1096/fj.03-0687fje.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionB-LymphocytesCalciumCalcium SignalingCell DivisionCell Line, TransformedCodon, NonsenseEndoplasmic ReticulumGentamicinsHumansIon TransportKidneyMembrane ProteinsMutation, MissenseOrgan SpecificityPlatelet Activating FactorPoint MutationPolycystic Kidney, Autosomal DominantProteinsRNA, MessengerSuppression, GeneticTRPP Cation ChannelsConceptsPlatelet-activating factorAutosomal dominant polycystic kidney disease patientsPolycystic kidney disease patientsKidney disease patientsCell proliferationPolycystin-2B lymphoblastoid cellsDisease patientsADPKD patientsB-LCLIntracellular Ca2PKD2 mutationsPC2 levelsKidney epitheliumPatientsChannel activityLymphoblastoid cellsAminoglycoside antibioticsKidney cellsImportant regulatorHEK293 cellsPKD2 geneFunction activityCa2PKD genesCalcium Dependence of Polycystin-2 Channel Activity Is Modulated by Phosphorylation at Ser812 *
Cai Y, Anyatonwu G, Okuhara D, Lee KB, Yu Z, Onoe T, Mei CL, Qian Q, Geng L, Wiztgall R, Ehrlich BE, Somlo S. Calcium Dependence of Polycystin-2 Channel Activity Is Modulated by Phosphorylation at Ser812 *. Journal Of Biological Chemistry 2004, 279: 19987-19995. PMID: 14742446, DOI: 10.1074/jbc.m312031200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBiotinylationCalciumCasein Kinase IICell MembraneDNA, ComplementaryEndoplasmic ReticulumGenes, DominantGlutathione TransferaseGlycosylationMembrane ProteinsMiceMice, Inbred BALB CMicroscopy, FluorescenceMutationPhosphatesPhosphorylationPrecipitin TestsProtein Serine-Threonine KinasesProtein Structure, TertiaryReverse Transcriptase Polymerase Chain ReactionSerineTime FactorsTRPP Cation ChannelsConceptsPolycystin-2Non-phosphorylated formChannel activityCation channelsCultured epithelial cellsActivation/inactivationPolycystic kidney diseaseProtein phosphorylationSubstitution mutantsNon-selective cation channelsConstitutive phosphorylationDivalent cation channelsPolycystin-1Substrate domainEndoplasmic reticulumPhosphorylationSingle-channel studiesVivo analysisControl cellsEpithelial cellsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseOpen probabilityCellsCK2
2003
Analysis of the Polycystins in Aortic Vascular Smooth Muscle Cells
Qian Q, Li M, Cai Y, Ward CJ, Somlo S, Harris PC, Torres VE. Analysis of the Polycystins in Aortic Vascular Smooth Muscle Cells. Journal Of The American Society Of Nephrology 2003, 14: 2280-2287. PMID: 12937304, DOI: 10.1097/01.asn.0000080185.38113.a3.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseVascular smooth muscle cellsSmooth muscle cellsAortic vascular smooth muscle cellsMuscle cellsSarcoplasmic reticulumCause of deathDominant polycystic kidney diseasePolycystic kidney diseasePolycystin-2Polycystin-1Kidney diseaseVascular phenotypeImmuno-gold electron microscopyADPKD proteinsTriton-X extractionPresent studyVivo interactionDense plaquesCell surface biotinylationCell surfacePlasma membranePolycystinsCellsSurface localizationPolycystin-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
Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases.
Obermüller N, Cai Y, Kränzlin B, Thomson RB, Gretz N, Kriz W, Somlo S, Witzgall R. Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases. Journal Of The American Society Of Nephrology 2002, 13: 1855-64. PMID: 12089381, DOI: 10.1097/01.asn.0000018402.33620.c7.Peer-Reviewed Original ResearchConceptsPolycystic kidney diseaseAutosomal dominant polycystic kidney diseaseKidney diseaseRenal failureDistal tubulesProximal tubulesIschemic acute renal failureCyst formationAcute renal failureAutosomal recessive polycystic kidney diseaseChronic renal failureRenal tubular diseaseCyst-lining cellsBasal compartmentPolycystin-2Renal injuryAcute injuryTubular diseaseKidney tissueAltered expression patternsPronounced upregulationNative kidney tissueS3 segmentDiseaseInjuryExpression of PKD1 and PKD2 Transcripts and Proteins in Human Embryo and during Normal Kidney Development
Chauvet V, Qian F, Boute N, Cai Y, Phakdeekitacharoen B, Onuchic LF, Attié-Bitach T, Guicharnaud L, Devuyst O, Germino GG, Gubler MC. Expression of PKD1 and PKD2 Transcripts and Proteins in Human Embryo and during Normal Kidney Development. American Journal Of Pathology 2002, 160: 973-983. PMID: 11891195, PMCID: PMC1867156, DOI: 10.1016/s0002-9440(10)64919-x.Peer-Reviewed Original ResearchConceptsPolycystin-1Kidney developmentPolycystin-2Expression patternsPKD1 expressionHuman genetic disordersLarge transmembrane proteinCell-matrix interactionsNormal kidney developmentMutations of PKD1Expression of PKD1Northern blot analysisGenes decreasesTransmembrane proteinHuman embryogenesisEndodermal derivativesSpatiotemporal expressionUreteric budPKD1 transcriptPKD2Transmembrane glycoproteinTranscriptsPKD1Nephron developmentProteinPolycystin-2 is an intracellular calcium release channel
Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S. Polycystin-2 is an intracellular calcium release channel. Nature Cell Biology 2002, 4: 191-197. PMID: 11854751, DOI: 10.1038/ncb754.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium ChannelsCalcium SignalingEndoplasmic ReticulumHumansIn Vitro TechniquesKidneyLLC-PK1 CellsMembrane PotentialsMembrane ProteinsMiceMice, Inbred C57BLMutationMutation, MissensePolycystic Kidney, Autosomal DominantRecombinant ProteinsSequence DeletionSignal TransductionSwineTRPP Cation ChannelsConceptsAutosomal dominant polycystic kidney diseaseIntracellular calcium release channelsPolycystic kidney diseaseCalcium release channelKidney diseaseTransient receptor potential channelsIntracellular calcium releaseDominant polycystic kidney diseaseRelease channelCalcium release signalsPolycystin-2 functionsType 2 autosomal dominant polycystic kidney diseaseCalcium releasePolycystin-2Single-channel studiesEpithelial cellsPotential channelsDiseaseMissense mutationsRelease signalsCarboxy-terminal truncationDisease-causing missense mutations
2000
Cloning and Characterization of the Murine Pkd2 Promoter
Park J, Li L, Cai Y, Hayashi T, Dong F, Maeda Y, Rubin C, Somlo S, Wu G. Cloning and Characterization of the Murine Pkd2 Promoter. Genomics 2000, 66: 305-312. PMID: 10873385, DOI: 10.1006/geno.2000.6197.Peer-Reviewed Original ResearchAnimalsBase SequenceCell LineCloning, MolecularCodon, InitiatorExonsGene Expression RegulationHumansIntronsMembrane ProteinsMiceMutagenesis, Site-DirectedPolycystic Kidney, Autosomal DominantPromoter Regions, GeneticSequence DeletionSequence Homology, Nucleic AcidTranscription, GeneticTransfectionTRPP Cation ChannelsCardiac defects and renal failure in mice with targeted mutations in Pkd2
Wu G, Markowitz G, Li L, D'Agati V, Factor S, Geng L, Tibara S, Tuchman J, Cai Y, Hoon Park J, van Adelsberg J, Hou H, Kucherlapati R, Edelmann W, Somlo S. Cardiac defects and renal failure in mice with targeted mutations in Pkd2. Nature Genetics 2000, 24: 75-78. PMID: 10615132, DOI: 10.1038/71724.Peer-Reviewed Original ResearchConceptsPolycystin-2True null mutationEmbryonic day 13.5Liver cyst formationSomatic rearrangementsNull mutationNull allelesProtein productsUnstable alleleTargeted mutationsPKD2Cardiac septationCyst formationRenal failureDay 13.5MutationsADPKD phenotypeKidney cystsAllelesLong-term survivalFirst indicationDeleterious effectsCalcium channelsMouse modelClinical manifestations
1999
The rat Pkd2 protein assumes distinct subcellular distributions in different organs
Obermüller N, Gallagher A, Cai Y, Gassler N, Gretz N, Somlo S, Witzgall R. The rat Pkd2 protein assumes distinct subcellular distributions in different organs. American Journal Of Physiology 1999, 277: f914-f925. PMID: 10600939, DOI: 10.1152/ajprenal.1999.277.6.f914.Peer-Reviewed Original ResearchConceptsPKD2 proteinDifferent cellular compartmentsDistinct subcellular distributionCellular compartmentsBasolateral distributionExpression patternsCytoplasmic locationSubcellular distributionPKD2 geneWidespread expressionCellular distributionAdrenal glandProteinSmooth muscle cellsSalivary glandsMuscle cellsPKD2Autosomal dominant polycystic kidney diseasePolycystic kidney diseaseDifferent organsRenal distal tubulesMutationsIndividual organsDifferent rat organsPKD2 mutationsAberrant splicing in the PKD2 gene as a cause of polycystic kidney disease.
Reynolds DM, Hayashi T, Cai Y, Veldhuisen B, Watnick TJ, Lens XM, Mochizuki T, Qian F, Maeda Y, Li L, Fossdal R, Coto E, Wu G, Breuning MH, Germino GG, Peters DJ, Somlo S. Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease. Journal Of The American Society Of Nephrology 1999, 10: 2342-51. PMID: 10541293, DOI: 10.1681/asn.v10112342.Peer-Reviewed Original ResearchConceptsPolycystin-2Mutant polycystin-2Future functional studiesNovel intragenic polymorphismsFrame splice variantsMissense variantsSingle base substitution mutationsPolycystin-2 proteinCryptic splice siteAutosomal dominant polycystic kidney diseaseBase substitution mutationsTransmembrane spansSingle base substitutionPolycystic kidney diseaseSplicing signalsSubunit functionAberrant splicingLymphoblast RNAMutant chromosomesSplice siteSubstitution mutationsPKD2 geneThird mutationBase substitutionsSplice variantsIdentification and Characterization of Polycystin-2, thePKD2 Gene Product*
Cai Y, Maeda Y, Cedzich A, Torres V, Wu G, Hayashi T, Mochizuki T, Park J, Witzgall R, Somlo S. Identification and Characterization of Polycystin-2, thePKD2 Gene Product*. Journal Of Biological Chemistry 1999, 274: 28557-28565. PMID: 10497221, DOI: 10.1074/jbc.274.40.28557.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum localizationPolycystin-2Gene productsPutative phosphorylation sitesProtein binding partnersProtein disulfide isomerasePKD2 gene productImmunofluorescent cell stainingIntegral membrane glycoproteinSubcellular fractionation studiesAutosomal dominant polycystic kidney diseaseEndo H resistanceGolgi proteinsPhosphorylation sitesSecond geneBinding partnerTruncation mutantsTranslation productsPlasma membraneHigh-mannose oligosaccharidesAcid regionEndoplasmic reticulumIntact cellsH resistanceMembrane glycoproteinsPolycystin-2 expression is developmentally regulated
Markowitz G, Cai Y, Li L, Wu G, Ward L, Somlo S, D’Agati V. Polycystin-2 expression is developmentally regulated. American Journal Of Physiology 1999, 277: f17-f25. PMID: 10409293, DOI: 10.1152/ajprenal.1999.277.1.f17.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium ChannelsEmbryo, MammalianKidneyMembrane ProteinsMiceTRPP Cation ChannelsConceptsPKD2 expressionMultiple mesenchymal tissuesLow-level stainingPostnatal day 14Low-intensity stainingRed blood cell precursorsPolycystin-2 expressionMultiple endocrine organsBlood cell precursorsAdrenal cortexEndocrine organDistal tubulesSmooth muscleProximal tubulesDay 14Day E12.5Adult patternBasolateral stainingCell precursorsMesenchymal tissueAdult kidneyOrgan-specific functionsEmbryonic dayStrong expressionStainingMutations in autosomal dominant polycystic kidney disease 2 gene: Reduced expression of PKD2 protein in lymphoblastoid cells
Aguiari G, Manzati E, Penolazzi L, Micheletti F, Augello G, De Vitali E, Cappelli G, Cai Y, Reynolds D, Somlo S, Piva R, del Senno L. Mutations in autosomal dominant polycystic kidney disease 2 gene: Reduced expression of PKD2 protein in lymphoblastoid cells. American Journal Of Kidney Diseases 1999, 33: 880-885. PMID: 10213643, DOI: 10.1016/s0272-6386(99)70420-8.Peer-Reviewed Original ResearchConceptsPolycystic kidney disease 2 (PKD2) geneMembrane-spanning domainsIntegral membrane proteinsLymphoblastoid cellsFirst extracellular loopAutosomal dominant polycystic kidney diseasePKD2 proteinMembrane proteinsRestriction enzyme analysisCommon genetic diseaseLymphoblastoid cell linesProtein productsMutant allelesExtracellular loopWestern blot analysisPKD2 genePolymerase chain reactionGenetic diseasesNormal proteinAmino acidsMessenger RNA levelsNonsense mutationFrameshift mutationGenesProtein
1998
Identification ofPKD2L,a HumanPKD2-Related Gene: Tissue-Specific Expression and Mapping to Chromosome 10q25
Wu G, Hayashi T, Park J, Dixit M, Reynolds D, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S. Identification ofPKD2L,a HumanPKD2-Related Gene: Tissue-Specific Expression and Mapping to Chromosome 10q25. Genomics 1998, 54: 564-568. PMID: 9878261, DOI: 10.1006/geno.1998.5618.Peer-Reviewed Original ResearchAmino Acid SequenceBlotting, NorthernCalcium ChannelsChromosomes, Human, Pair 10Cloning, MolecularExpressed Sequence TagsGene Expression RegulationGenetic MarkersHumansLiverLiver DiseasesMembrane GlycoproteinsMembrane ProteinsMolecular Sequence DataOrgan SpecificityPhosphoproteinsPolycystic Kidney, Autosomal DominantPolymorphism, GeneticReceptors, Cell SurfaceRetinaSequence Homology, Amino AcidTissue DistributionTRPP Cation ChannelsSomatic Inactivation of Pkd2 Results in Polycystic Kidney Disease
Wu G, D'Agati V, Cai Y, Markowitz G, Park J, Reynolds D, Maeda Y, Le T, Hou H, Kucherlapati R, Edelmann W, Somlo S. Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease. Cell 1998, 93: 177-188. PMID: 9568711, DOI: 10.1016/s0092-8674(00)81570-6.Peer-Reviewed Original ResearchConceptsCellular recessive mechanismIntragenic homologous recombinationExon 1True null alleleMutant exon 1Somatic inactivationPkd2 resultsRenal cyst formationPKD2 proteinPolycystic kidney diseaseHomologous recombinationNull allelesHuman phenotypesPKD2 expressionUnstable alleleSomatic lossPKD2Autosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseMutationsGermline mutationsRecessive mechanismAllelesInactivationCyst formation