2021
Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death
Decuypere JP, Van Giel D, Janssens P, Dong K, Somlo S, Cai Y, Mekahli D, Vennekens R. Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death. International Journal Of Molecular Sciences 2021, 22: 13511. PMID: 34948309, PMCID: PMC8706473, DOI: 10.3390/ijms222413511.Peer-Reviewed Original ResearchConceptsProximal tubular epithelial cellsAutosomal dominant polycystic kidney diseaseEarly-stage ADPKD patientsCell deathPC2 expressionDominant polycystic kidney diseaseTubular epithelial cellsRenal cell survivalPolycystin-1Polycystic kidney diseaseCell survivalPolycystin-2Basal autophagyAutophagic cell survivalCell death resistanceADPKD progressionKidney diseaseADPKD patientsLess cell deathPC1 levelsChronic starvationHealthy individualsDuct cellsEpithelial cellsDeath
2016
Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells
de Stephanis L, Bonon A, Varani K, Lanza G, Gafà R, Pinton P, Pema M, Somlo S, Boletta A, Aguiari G. Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells. Clinical And Experimental Nephrology 2016, 21: 203-211. PMID: 27278932, PMCID: PMC5496448, DOI: 10.1007/s10157-016-1289-1.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine A3 Receptor AgonistsAnimalsCell LineCell ProliferationCREB-Binding ProteinCyclic AMPDisease Models, AnimalDrug SynergismDrug Therapy, CombinationExtracellular Signal-Regulated MAP KinasesGenetic Predisposition to DiseaseHumansKidneyMice, Inbred C57BLMice, KnockoutPhenotypePhosphorylationPolycystic Kidney, Autosomal DominantProtein Kinase InhibitorsSignal TransductionSirolimusTime FactorsTOR Serine-Threonine KinasesTRPP Cation ChannelsConceptsCl-IBADPKD patientsCell proliferationADPKD cellsActivation of A3ARCell growthAgonist Cl-IBPolycystin-1MethodsThe inhibitionCombined sequential treatmentRenal functionKidney weightAbnormal cell proliferationERK kinase activityRenal pathologyA3 receptorsInhibition of CREBKidney tissueKinase activityPolycystin-2Marked reductionDirect cell countingKidney cystsMutations of PKD1ERK phosphorylation
2015
Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity
Fedeles SV, So JS, Shrikhande A, Lee SH, Gallagher AR, Barkauskas CE, Somlo S, Lee AH. Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity. Journal Of Clinical Investigation 2015, 125: 1955-1967. PMID: 25844898, PMCID: PMC4463201, DOI: 10.1172/jci78863.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalDNA HelicasesDNA-Binding ProteinsEndoribonucleasesFemaleGlucosidasesIntracellular Signaling Peptides and ProteinsKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMolecular ChaperonesPolycystic Kidney, Autosomal DominantPolycystic Kidney, Autosomal RecessiveProtein Serine-Threonine KinasesProtein Structure, TertiaryReceptors, G-Protein-CoupledRecombinant Fusion ProteinsRegulatory Factor X Transcription FactorsRNA SplicingRNA, Small InterferingRNA-Binding ProteinsTranscription FactorsTransfectionTRPP Cation ChannelsUnfolded Protein ResponseX-Box Binding Protein 1ConceptsG protein-coupled receptor proteolysis siteCyst formationPolycystic liver diseaseGPS cleavagePolycystin-1IRE1α-XBP1 branchMurine genetic modelsPolycystic kidney phenotypeLiver diseasePolycystic diseaseCystic diseaseDisease manifestationsMurine modelDisease severityKidney phenotypeXBP1 activationUnfolded protein response pathwayDiseaseXBP1 overexpressionPC1 functionsProtein response pathwayEnforced expressionMiceXBP1Activation of XBP1
2014
Altered trafficking and stability of polycystins underlie polycystic kidney disease
Cai Y, Fedeles SV, Dong K, Anyatonwu G, Onoe T, Mitobe M, Gao JD, Okuhara D, Tian X, Gallagher AR, Tang Z, Xie X, Lalioti MD, Lee AH, Ehrlich BE, Somlo S. Altered trafficking and stability of polycystins underlie polycystic kidney disease. Journal Of Clinical Investigation 2014, 124: 5129-5144. PMID: 25365220, PMCID: PMC4348948, DOI: 10.1172/jci67273.Peer-Reviewed Original ResearchConceptsG-protein-coupled receptor proteolytic sitePolycystic kidney diseaseKidney diseaseGPS cleavageAutosomal dominant polycystic kidney diseaseMissense mutationsDominant polycystic kidney diseasePolycystin-1Polycystin-2Murine modelSevere formPathogenic missense mutationsPKD1 mutationsCOOH-terminal fragmentDiseaseMissense variantsExpression levelsFunctional assaysCell-based systemsAltered traffickingN-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*
Hofherr A, Wagner C, Fedeles S, Somlo S, Köttgen M. N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*. Journal Of Biological Chemistry 2014, 289: 14854-14867. PMID: 24719335, PMCID: PMC4031537, DOI: 10.1074/jbc.m114.562264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsparagineBinding SitesBlotting, WesternCell LineCells, CulturedGlucosidasesGlycosylationHEK293 CellsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMass SpectrometryMiceMice, KnockoutMicroscopy, FluorescenceMutationPolycystic Kidney, Autosomal DominantProtein Serine-Threonine KinasesProteolysisPyruvate Dehydrogenase Acetyl-Transferring KinaseConceptsGlucosidase IINon-catalytic β-subunitsProtein expressionFirst extracellular loopAutosomal dominant polycystic liver diseaseEfficient biogenesisGenetic interactionsMembrane proteinsBiochemical approachesN-glycosylationGenetic approachesTRPP2Glycosylation sitesBiological roleLysosomal degradationΒ-subunitChemical inhibitionBiogenesisExtracellular loopNonselective cation channelsIon channelsBiological importanceGlycosylationCation channelsProtein levels