2019
Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2
Kuo IY, Brill AL, Lemos FO, Jiang JY, Falcone JL, Kimmerling EP, Cai Y, Dong K, Kaplan DL, Wallace DP, Hofer AM, Ehrlich BE. Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2. Science Signaling 2019, 12 PMID: 31064883, PMCID: PMC6855602, DOI: 10.1126/scisignal.aat7397.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumPC2 knockdownMitochondrial CaCell culture modelKnockdown of Mfn2Polycystin-2 functionsHuman ADPKD kidneysAutosomal dominant polycystic kidney diseaseKey mitochondrial proteinsAberrant cell proliferationMitochondria-ER contactsCell proliferationER-mitochondrial interfaceKidney cystsIntimate functional relationshipNumerous fluid-filled cystsMitochondrial proteinsCyst-lining epithelial cellsMitofusin 2 expressionCulture modelPolycystin-2Knockdown cellsMitochondrial biogenesisMitofusin 2Mitochondrial respiration
2010
Polycystin-2 Activation by Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Requires Its Direct Association with the Inositol 1,4,5-Trisphosphate Receptor in a Signaling Microdomain*
Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, De Smedt H. Polycystin-2 Activation by Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Requires Its Direct Association with the Inositol 1,4,5-Trisphosphate Receptor in a Signaling Microdomain*. Journal Of Biological Chemistry 2010, 285: 18794-18805. PMID: 20375013, PMCID: PMC2881802, DOI: 10.1074/jbc.m109.090662.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseGlutathione S-transferase pulldown experimentsEndoplasmic reticulumTrisphosphate receptorAgonist-induced intracellularTerminal ligand-binding domainMouse renal epithelial cellsTerminal cytoplasmic tailLigand-binding domainAdenoviral expression systemRenal epithelial cellsSignaling microdomainPathological mutantsPulldown experimentsTrisphosphate-induced Ca2Cytoplasmic tailAcidic clusterPolycystin-1Polycystin-2TRPP2Epithelial cellsExpression system
2004
Calcium 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
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
1999
Identification 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 glycoproteins