2023
SLC26A1 is a major determinant of sulfate homeostasis in humans
Pfau A, López-Cayuqueo K, Scherer N, Wuttke M, Wernstedt A, Fassrainer D, Smith D, van de Kamp J, Ziegeler K, Eckardt K, Luft F, Aronson P, Köttgen A, Jentsch T, Knauf F. SLC26A1 is a major determinant of sulfate homeostasis in humans. Journal Of Clinical Investigation 2023, 133: e161849. PMID: 36719378, PMCID: PMC9888379, DOI: 10.1172/jci161849.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnion Transport ProteinsAntiportersHomeostasisHumansIon TransportMiceMice, KnockoutSulfate TransportersSulfatesConceptsSulfate homeostasisIntervertebral disc disordersWhole-exome sequencingMajor determinantBack painPatient presentingMusculoskeletal healthDisc disordersPlasma sulfateSulfate reabsorptionFunctional expression assaysCartilage healthHomozygous mutationPotential targetPopulation studiesNumerous physiological processesRecent evidenceExome analysisHomeostasisHyposulfatemiaExpression assaysPivotal roleClinical geneticsAdditional variantsHumans
2022
Dominant negative mutation in oxalate transporter SLC26A6 associated with enteric hyperoxaluria and nephrolithiasis
Cornière N, Thomson RB, Thauvin S, Villoutreix BO, Karp S, Dynia DW, Burlein S, Brinkmann L, Badreddine A, Dechaume A, Derhourhi M, Durand E, Vaillant E, Froguel P, Chambrey R, Aronson PS, Bonnefond A, Eladari D. Dominant negative mutation in oxalate transporter SLC26A6 associated with enteric hyperoxaluria and nephrolithiasis. Journal Of Medical Genetics 2022, 59: 1035-1043. PMID: 35115415, PMCID: PMC9346097, DOI: 10.1136/jmedgenet-2021-108256.Peer-Reviewed Original ResearchMeSH KeywordsAntiportersCalciumCalcium OxalateHumansHyperoxaluriaMutationNephrolithiasisOxalatesSulfate TransportersConceptsRare heterozygous missense mutationsWild-type proteinStrong dominant-negative effectDominant negative effectDominant negative mutationMembrane surface expressionOxalate transporter SLC26A6Calcium oxalate nephrolithiasisCotransfection studiesOxalate transporterSilico analysisNegative mutationTransport activityMissense mutationsHeterozygous missense mutationEnteric hyperoxaluriaComplex multifactorial diseaseMutationsOxalate nephrolithiasisHuman populationSurface expressionCell culturesUrinary oxalate excretionMajor risk factorGenetic factors
2020
Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease
Neumeier LI, Thomson RB, Reichel M, Eckardt KU, Aronson PS, Knauf F. Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease. Journal Of The American Society Of Nephrology 2020, 31: 1987-1995. PMID: 32660969, PMCID: PMC7461683, DOI: 10.1681/asn.2020010105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiportersDisease Models, AnimalIntestinal MucosaMaleMiceMice, Inbred C57BLOxalatesRenal Insufficiency, ChronicSulfate TransportersConceptsEnteric oxalate secretionPlasma oxalate concentrationOxalate secretionModel of CKDChronic kidney diseaseIntestine of miceWild-type miceHealthy kidney functionOxalate clearanceWestern blot analysisKidney injuryKidney functionOxalate excretionWeekly injectionsKidney diseaseCKD modelExtrarenal clearanceOxalate transporter SLC26A6CKDMurine modelSignificant elevationOxalate homeostasisTransporter expressionMiceProtein expression
2018
Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice
Knauf F, Velazquez H, Pfann V, Jiang Z, Aronson PS. Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice. American Journal Of Physiology. Renal Physiology 2018, 316: f128-f133. PMID: 30427220, PMCID: PMC6383200, DOI: 10.1152/ajprenal.00309.2018.Peer-Reviewed Original ResearchConceptsWild-type miceNaCl homeostasisBlood pressureProximal tubulesFree-flow micropuncture studiesSurface proximal tubulesLow-salt dietMean blood pressureLower blood pressureUrine flow rateLack of effectFurosemide infusionNet renal secretionSodium excretionUrine oxalateFractional excretionMicropuncture studiesNaCl deliveryRenal secretionApical membrane ClExchanger SLC26A6MiceRenal NaClNaCl transportHomeostasis
2016
N-glycosylation critically regulates function of oxalate transporter SLC26A6
Thomson RB, Thomson CL, Aronson PS. N-glycosylation critically regulates function of oxalate transporter SLC26A6. American Journal Of Physiology - Cell Physiology 2016, 311: c866-c873. PMID: 27681177, PMCID: PMC5206297, DOI: 10.1152/ajpcell.00171.2016.Peer-Reviewed Original ResearchConceptsPlasma membraneIntegral membrane proteinsCell surface deliverySLC26A6 functionTissue-specific differencesGlycosylation mutantsMembrane proteinsN-glycosylationSurface deliveryBiotinylation studiesOxalate transporterOxalate homeostasisSecond extracellular loopExtracellular loopIntact cellsEnzymatic deglycosylation studiesTransport activityEnzymatic deglycosylationFunctional studiesDeglycosylation studiesGlycosylationPutative second extracellular loopTransport functionFunctional significanceEssential roleLoss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion
Knauf F, Thomson RB, Heneghan JF, Jiang Z, Adebamiro A, Thomson CL, Barone C, Asplin JR, Egan ME, Alper SL, Aronson PS. Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion. Journal Of The American Society Of Nephrology 2016, 28: 242-249. PMID: 27313231, PMCID: PMC5198290, DOI: 10.1681/asn.2016030279.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiportersCalcium OxalateCystic Fibrosis Transmembrane Conductance RegulatorHyperoxaluriaIntestinal MucosaMiceMice, KnockoutSulfate TransportersConceptsIntestinal oxalate secretionWild-type miceCystic fibrosisIntestinal tissueOxalate secretionIncidence of hyperoxaluriaCalcium oxalate stone formationNet intestinal absorptionOxalate stone formationCoexpression of CFTRIntestinal transport processesWestern blot analysisOxalate absorptionMouse modelIntestinal absorptionGlucose absorptionUssing chambersStone formationFibrosisMiceSecretionReduced expressionCystic fibrosis transmembrane conductance regulator (CFTR) geneHyperoxaluriaPatients
2013
Overexpression of Pendrin in Intercalated Cells Produces Chloride-Sensitive Hypertension
Jacques T, Picard N, Miller RL, Riemondy KA, Houillier P, Sohet F, Ramakrishnan SK, Büsst CJ, Jayat M, Cornière N, Hassan H, Aronson PS, Hennings JC, Hübner CA, Nelson RD, Chambrey R, Eladari D. Overexpression of Pendrin in Intercalated Cells Produces Chloride-Sensitive Hypertension. Journal Of The American Society Of Nephrology 2013, 24: 1104-1113. PMID: 23766534, PMCID: PMC3699825, DOI: 10.1681/asn.2012080787.Peer-Reviewed Original ResearchConceptsDistal nephronTransgenic miceSame sodium intakeHigh salt intakeCause of hypertensionHigh-salt dietSodium-driven chloride/bicarbonate exchangerNet NaCl absorptionArterial hypertensionSalt intakeSodium intakeEpithelial sodium channel ENaCPathogenic roleNormal miceHypertensionRenal absorptionExchanger pendrinPrimary abnormalityVascular volumeAppropriate downregulationIntercalated cellsChloride absorptionSodium channel ENaCActivity of transportersPrimary activation
2012
Urinary Metabolic Phenotyping the slc26a6 (Chloride–Oxalate Exchanger) Null Mouse Model
Garcia-Perez I, Villaseñor A, Wijeyesekera A, Posma JM, Jiang Z, Stamler J, Aronson P, Unwin R, Barbas C, Elliott P, Nicholson J, Holmes E. Urinary Metabolic Phenotyping the slc26a6 (Chloride–Oxalate Exchanger) Null Mouse Model. Journal Of Proteome Research 2012, 11: 4425-4435. PMID: 22594923, PMCID: PMC4028149, DOI: 10.1021/pr2012544.Peer-Reviewed Original ResearchConceptsRenal stone diseaseStone diseaseNull miceUrinary metabolic signaturesBlood pressure controlWild-type miceNull mouse modelRenal stone formationRenal proximal tubulesUrinary metabolicUrinary metabolomeClear metabolic differentiationSodium homeostasisRenal stonesType miceMouse modelUrinary metabolitesOxalate balanceUrinary profilesProximal tubulesPressure controlStone formationExchanger SLC26A6Metabolic signaturesPathological processesSat1 is dispensable for active oxalate secretion in mouse duodenum
Ko N, Knauf F, Jiang Z, Markovich D, Aronson PS. Sat1 is dispensable for active oxalate secretion in mouse duodenum. American Journal Of Physiology - Cell Physiology 2012, 303: c52-c57. PMID: 22517357, PMCID: PMC3404526, DOI: 10.1152/ajpcell.00385.2011.Peer-Reviewed Original ResearchConceptsCalcium oxalate stonesMouse duodenumOxalate secretionOxalate stonesIntestinal oxalate secretionIntestinal oxalate transportSecretory fluxSAT1 expressionDisulfonic stilbene DIDSDuodenumTransporter 1SecretionMiceHyperoxalemiaBasolateral solutionHyperoxaluriaBasolateral transportersBicarbonate productionOxalate transportBasolateral membraneSAT1Apical membraneComplete removalMedium concentration
2011
Net Intestinal Transport of Oxalate Reflects Passive Absorption and SLC26A6-mediated Secretion
Knauf F, Ko N, Jiang Z, Robertson WG, Van Itallie CM, Anderson JM, Aronson PS. Net Intestinal Transport of Oxalate Reflects Passive Absorption and SLC26A6-mediated Secretion. Journal Of The American Society Of Nephrology 2011, 22: 2247-2255. PMID: 22021714, PMCID: PMC3250206, DOI: 10.1681/asn.2011040433.Peer-Reviewed Original ResearchCholinergic signaling inhibits oxalate transport by human intestinal T84 cells
Hassan HA, Cheng M, Aronson PS. Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells. American Journal Of Physiology - Cell Physiology 2011, 302: c46-c58. PMID: 21956166, PMCID: PMC3328906, DOI: 10.1152/ajpcell.00075.2011.Peer-Reviewed Original ResearchConceptsC-SrcT84 cellsHuman intestinal cell line T84PKC-δ inhibitor rottlerinSrc inhibitor PP2Intestinal cell line T84Human intestinal T84 cellsSurface expressionMuscarinic receptorsRegulation downstreamInhibitor PP2Phosphorylation studiesBiotinylation studiesInhibitor rottlerinKnockdown studiesPharmacological inhibitorsIntestinal T84 cellsIntestinal oxalate secretionPhospholipase CIntestinal ion transportPKC activationSignificant translocationCalcium oxalate urolithiasisPKCAnion exchanger SLC26A6
2010
Role of SLC26A6-mediated Cl⁻-oxalate exchange in renal physiology and pathophysiology.
Aronson PS. Role of SLC26A6-mediated Cl⁻-oxalate exchange in renal physiology and pathophysiology. Journal Of Nephrology 2010, 23 Suppl 16: s158-64. PMID: 21170874.Commentaries, Editorials and LettersMeSH KeywordsAnimalsChloridesHomeostasisHumansKidney Tubules, ProximalMembrane Transport ProteinsMiceOxalatesSulfate TransportersUrolithiasisConceptsNull miceCalcium oxalate urolithiasisProximal tubule cellsStone riskAnimal modelsOxalate urolithiasisProximal tubulesOxalate homeostasisTubule cellsApical membrane ClHyperoxaluriaRenal physiologyOxalate exchangeMiceExchange activitySubsequent studiesAnion transportersPossible mechanismHyperoxalemiaPatientsPathophysiologyUrolithiasisStriking phenotypeReabsorption
2009
Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent
Bai JP, Surguchev A, Montoya S, Aronson PS, Santos-Sacchi J, Navaratnam D. Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent. Biophysical Journal 2009, 96: 3179-3186. PMID: 19383462, PMCID: PMC2718310, DOI: 10.1016/j.bpj.2008.12.3948.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnalysis of VarianceAnimalsAnion Transport ProteinsAntiportersCarbon RadioisotopesChloridesCHO CellsCricetinaeCricetulusElectric CapacitanceFormatesGerbillinaeIon TransportMiceMutation, MissenseOxalatesPatch-Clamp TechniquesSalicylatesSulfate TransportersConceptsClosest phylogenetic relativesTransmembrane regionSLC26 anion transporter familyMammalian outer hair cellsMembrane protein prestinPrestin's motor functionAnion transportPhylogenetic relativesAnion transporter familyTransporter familyProtein prestinChloride-binding siteGating charge movementPrestinCharge movementHair cellsOuter hair cellsResiduesMechanistic conceptsVoltage sensingTransport capabilityCellsVoltage sensorPrevious observationsUptake studies
2008
Phenotypic and Functional Analysis of Human SLC26A6 Variants in Patients With Familial Hyperoxaluria and Calcium Oxalate Nephrolithiasis
Monico CG, Weinstein A, Jiang Z, Rohlinger AL, Cogal AG, Bjornson BB, Olson JB, Bergstralh EJ, Milliner DS, Aronson PS. Phenotypic and Functional Analysis of Human SLC26A6 Variants in Patients With Familial Hyperoxaluria and Calcium Oxalate Nephrolithiasis. American Journal Of Kidney Diseases 2008, 52: 1096-1103. PMID: 18951670, PMCID: PMC2710965, DOI: 10.1053/j.ajkd.2008.07.041.Peer-Reviewed Original ResearchConceptsPrimary hyperoxaluria type 1Oxalate transportMajor risk factorCalcium oxalate nephrolithiasisUrine oxalate levelsCalcium oxalate urolithiasisRare variantsHyperoxaluria type 1Calcium oxalate stonesAdditional missense variantsUrine oxalateOxalate excretionRisk factorsOxalate nephrolithiasisOxalate urolithiasisHyperoxaluriaAbstractTextAdult subjectsType 1Oxalate stonesPotential modifiersStudy designOxalate levelsGood healthMissense variants
2007
Specificity and Regulation of Renal Sulfate Transporters
Markovich D, Aronson PS. Specificity and Regulation of Renal Sulfate Transporters. Annual Review Of Physiology 2007, 69: 361-375. PMID: 17002596, DOI: 10.1146/annurev.physiol.69.040705.141319.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsCation Transport ProteinsHumansMembrane Transport ProteinsSodium Sulfate CotransporterSulfate TransportersSymportersConceptsProximal tubulesSulfate reabsorptionProximal tubular cellsRenal expressionApical membraneKnockout mouse studiesTubular cellsNet reabsorptionNaCl reabsorptionMouse studiesMajor roleReabsorptionSulfate homeostasisCFEXKidneyFamily membersPhysiological roleCurrent dataNormal cellular functionBasolateral membraneTubulesSLC26 family members
2006
Regulation of anion exchanger Slc26a6 by protein kinase C
Hassan HA, Mentone S, Karniski LP, Rajendran VM, Aronson PS. Regulation of anion exchanger Slc26a6 by protein kinase C. American Journal Of Physiology - Cell Physiology 2006, 292: c1485-c1492. PMID: 17151144, DOI: 10.1152/ajpcell.00447.2006.Peer-Reviewed Original ResearchMeSH KeywordsAcetophenonesAnimalsAnion Transport ProteinsAntiportersBenzopyransBiological Transport, ActiveCarbazolesCell MembraneChloridesCytoplasmEnzyme ActivationFemaleFormatesIn Vitro TechniquesIndolesMaleimidesMiceOocytesOxalatesProtein Kinase C-deltaProtein TransportSulfate TransportersTetradecanoylphorbol AcetateXenopusConceptsPKC activationOxalate secretionIntestinal oxalate secretionFormate exchangeRenal proximal tubulesAnion exchanger pendrinPancreatic ductExchanger pendrinProximal tubulesSmall intestineSLC26A6 expressionNaCl reabsorptionCalcium independentSimilar extentPotential rolePKC-delta activationProtein kinase CActivationSecretionSlc26a6Immunofluorescence microscopyXenopus oocytesPMAPhysiological significanceOocyte plasma membraneEssential roles of CFEX-mediated Cl−–oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis
Aronson PS. Essential roles of CFEX-mediated Cl−–oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis. Kidney International 2006, 70: 1207-1213. PMID: 16883319, DOI: 10.1038/sj.ki.5001741.Commentaries, Editorials and LettersAnimalsAntiportersCalcium OxalateChloride-Bicarbonate AntiportersChloridesDisease Models, AnimalFormatesHomeostasisHumansHyperoxaluriaImmunohistochemistryIntestinal AbsorptionIon ExchangeKidney Tubules, ProximalMiceMice, KnockoutModels, BiologicalNephrolithiasisOocytesOxalatesSodium ChlorideSulfate TransportersXenopusRole of SLC26‐Mediated Cl−/Base Exchange in Proximal Tubule NaCl Transport
Aronson PS. Role of SLC26‐Mediated Cl−/Base Exchange in Proximal Tubule NaCl Transport. Novartis Foundation Symposia 2006, 273: 148-163. PMID: 17120766, DOI: 10.1002/0470029579.ch10.Commentaries, Editorials and LettersCalcium oxalate urolithiasis in mice lacking anion transporter Slc26a6
Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nature Genetics 2006, 38: 474-478. PMID: 16532010, DOI: 10.1038/ng1762.Peer-Reviewed Original ResearchConceptsCalcium oxalate urolithiasisOxalate urolithiasisPlasma oxalate concentrationIntestinal oxalate secretionUrinary oxalate concentrationCommon urologic diseaseNet intestinal absorptionAnion exchanger SLC26A6Dietary oxalate restrictionSlc26a6-null miceSignificant hyperoxaluriaOxalate restrictionUrologic diseasesHigh incidenceIntestinal absorptionExchanger SLC26A6Mutant miceUrolithiasisMiceMajor constitutive roleNet absorptionOxalate secretionHyperoxaluriaOxalate concentrationEpithelial tissues
2005
Immunolocalization of anion transporter Slc26a7 in mouse kidney
Dudas PL, Mentone S, Greineder CF, Biemesderfer D, Aronson PS. Immunolocalization of anion transporter Slc26a7 in mouse kidney. American Journal Of Physiology. Renal Physiology 2005, 290: f937-f945. PMID: 16263805, DOI: 10.1152/ajprenal.00197.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnionsChloride-Bicarbonate AntiportersFluorescent Antibody TechniqueIon TransportKidney Tubules, ProximalLoop of HenleMiceSulfate TransportersConceptsThick ascending limbMouse kidneyProximal tubulesAscending limbThick ascending limb cellsLoop of HenleProximal tubule cellsSimilar staining patternExpression of SLC26A7Recent studiesTubule cellsNull miceNephron segmentsRat kidneyKidneyDifferent epitopesStaining patternMonoclonal antibodiesAntibodiesApical membrane transportersLimb cellsCOS-7 cellsImmunofluorescence microscopyLimbBasolateral surface