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 ResearchConceptsSulfate 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 ResearchConceptsEnteric 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 ResearchConceptsIntestinal 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
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 Research
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
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 LettersThe life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates
Knauf F, Mohebbi N, Teichert C, Herold D, Rogina B, Helfand S, Gollasch M, Luft FC, Aronson PS. The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates. Biochemical Journal 2006, 397: 25-29. PMID: 16608441, PMCID: PMC1479758, DOI: 10.1042/bj20060409.Peer-Reviewed Original ResearchConceptsExternal citrateKrebs cycle intermediatesXenopus oocytesSodium dicarboxylate cotransporterMammalian genesDrosophila melanogasterIndy mutantsLifespan extensionLongevity genesPlasma membraneSubstrate effluxExternal mediumSpecific transport mechanismsFunctional studiesSuccinate uptakeAddition of succinateEnergy metabolismIndyTransportable substratesGenesOocytesEffluxMelanogasterMutantsSuccinateCalcium 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 tissuesIon exchangers mediating Na+, HCO3 - and Cl- transport in the renal proximal tubule.
Aronson PS. Ion exchangers mediating Na+, HCO3 - and Cl- transport in the renal proximal tubule. Journal Of Nephrology 2006, 19 Suppl 9: s3-s10. PMID: 16736438.Commentaries, Editorials and LettersConceptsProximal tubulesNaCl absorptionApical membrane ClNull miceOxalate-sulfate exchangePendrin-null miceProximal tubule cellsBrush borderFormate exchangeRenal proximal tubulesSlc26a6-null miceAcid secretionPendrin expressionFunctional expression studiesTubule cellsNaCl reabsorptionCl absorptionBrush border membraneSulfate cotransportLines of evidenceExchanger isoformsTubulesMiceFamily membersBorder membrane
2005
Role of PDZK1 in membrane expression of renal brush border ion exchangers
Thomson RB, Wang T, Thomson BR, Tarrats L, Girardi A, Mentone S, Soleimani M, Kocher O, Aronson PS. Role of PDZK1 in membrane expression of renal brush border ion exchangers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13331-13336. PMID: 16141316, PMCID: PMC1201624, DOI: 10.1073/pnas.0506578102.Peer-Reviewed Original ResearchConceptsProximal tubulesExpression of NHE3Functional activityRole of PDZK1Protein PDZK1Reabsorption of NaBrush border expressionMammalian kidneyCFEXBrush border localizationMutant miceGST fusion proteinProtein expressionKidneyBrush border membrane proteinsExchanger NHE3Membrane expressionNHE3Brush borderBrush border membrane vesiclesPDZK1 interactionTubulesNormal expressionMembrane proteinsPDZK1
2004
Renal and intestinal transport defects in Slc26a6-null mice
Wang Z, Wang T, Petrovic S, Tuo B, Riederer B, Barone S, Lorenz JN, Seidler U, Aronson PS, Soleimani M. Renal and intestinal transport defects in Slc26a6-null mice. American Journal Of Physiology - Cell Physiology 2004, 288: c957-c965. PMID: 15574486, DOI: 10.1152/ajpcell.00505.2004.Peer-Reviewed Original ResearchConceptsWild-type miceProximal tubulesSlc26a6-null miceHCO3- secretionKidney proximal tubulesApical membrane ClNull miceBaseline rateNormal blood pressureCl-/formate exchangeBlood pressureKidney functionElectrolyte profileMucosal tissuesIntestinal physiologyUssing chambersSmall intestineMiceFluid absorptionNaCl absorptionStatistical significanceCl-/HCO3NaCl transportDuodenumTubules
2002
Specificity of Anion Exchange Mediated by Mouse Slc26a6*
Jiang Z, Grichtchenko II, Boron WF, Aronson PS. Specificity of Anion Exchange Mediated by Mouse Slc26a6*. Journal Of Biological Chemistry 2002, 277: 33963-33967. PMID: 12119287, DOI: 10.1074/jbc.m202660200.Peer-Reviewed Original ResearchConceptsProximal tubule cellsP-aminohippurateTubule cellsOxalate-sulfate exchangeTransport of oxalatePH recordingRenal tubular fluidTubular fluidVoltage-clamp measurementsBrush border membraneFormate exchangeOxalate exchangeMeasurement of uptakeClamp measurementsBorder membraneSlc26a6Two-electrode voltage clamp measurementsXenopus oocytesPresent studyHigh oxalate concentrationsApical membraneOocytesMouse orthologueCellsCFEX
2001
Identification of a chloride-formate exchanger expressed on the brush border membrane of renal proximal tubule cells
Knauf F, Yang C, Thomson R, Mentone S, Giebisch G, Aronson P. Identification of a chloride-formate exchanger expressed on the brush border membrane of renal proximal tubule cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 9425-9430. PMID: 11459928, PMCID: PMC55437, DOI: 10.1073/pnas.141241098.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmino Acid SequenceAnimalsAntiportersBase SequenceCloning, MolecularCOS CellsDNA PrimersDNA, ComplementaryFemaleKidney Tubules, ProximalMiceMice, Inbred C57BLMicroscopy, FluorescenceMicrovilliMolecular Sequence DataSodium-Phosphate Cotransporter Proteins, Type IIaXenopus laevis