2020
Disrupting polycystin-2 EF hand Ca2+ affinity does not alter channel function or contribute to polycystic kidney disease
Vien TN, Ng LCT, Smith JM, Dong K, Krappitz M, Gainullin VG, Fedeles S, Harris PC, Somlo S, DeCaen PG. Disrupting polycystin-2 EF hand Ca2+ affinity does not alter channel function or contribute to polycystic kidney disease. Journal Of Cell Science 2020, 133: jcs255562. PMID: 33199522, PMCID: PMC7774883, DOI: 10.1242/jcs.255562.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseDominant polycystic kidney diseaseChannel functionPhysiological membrane potentialsPolycystin-2Primary ciliaDuct cellsNew mouseChannel activityDiseaseIon channelsDistinct mutationsInternal CaMembrane potentialChannel regulationHand associationEF-hand Ca2Regulatory mechanismsMutationsMice
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 traffickingPolycystin-1: a master regulator of intersecting cystic pathways
Fedeles SV, Gallagher AR, Somlo S. Polycystin-1: a master regulator of intersecting cystic pathways. Trends In Molecular Medicine 2014, 20: 251-260. PMID: 24491980, PMCID: PMC4008641, DOI: 10.1016/j.molmed.2014.01.004.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseAutosomal recessive polycystic kidney diseaseAutosomal dominant polycystic liver diseasePolycystic kidney diseaseKidney diseasePolycystic liver diseaseRecessive polycystic kidney diseaseDominant polycystic kidney diseaseLiver diseasePolycystic diseaseCyst growthLethal monogenic disorderCyst formationTranslational implicationsDiseaseMonogenic disordersCausative genesCystic phenotypeRecent dataPolycystin-1Polycystin-2Master regulator