2014
Cyclic GMP Kinase II (cGKII) Inhibits NHE3 by Altering Its Trafficking and Phosphorylating NHE3 at Three Required Sites IDENTIFICATION OF A MULTIFUNCTIONAL PHOSPHORYLATION SITE*
Chen T, Kocinsky HS, Cha B, Murtazina R, Yang J, Tse CM, Singh V, Cole R, Aronson PS, de Jonge H, Sarker R, Donowitz M. Cyclic GMP Kinase II (cGKII) Inhibits NHE3 by Altering Its Trafficking and Phosphorylating NHE3 at Three Required Sites IDENTIFICATION OF A MULTIFUNCTIONAL PHOSPHORYLATION SITE*. Journal Of Biological Chemistry 2014, 290: 1952-1965. PMID: 25480791, PMCID: PMC4303652, DOI: 10.1074/jbc.m114.590174.Peer-Reviewed Original ResearchAnimalsBinding SitesCaco-2 CellsCell MembraneCyclic GMP-Dependent Protein Kinase Type IIDexamethasoneHumansIntestinal MucosaMass SpectrometryMiceMicrovilliMutagenesisPhosphorylationProtein Structure, TertiaryProtein TransportSerineSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSurface PropertiesTransfection
2013
Ezrin Is Required for the Functional Regulation of the Epithelial Sodium Proton Exchanger, NHE3
Hayashi H, Tamura A, Krishnan D, Tsukita S, Suzuki Y, Kocinsky HS, Aronson PS, Orlowski J, Grinstein S, Alexander RT. Ezrin Is Required for the Functional Regulation of the Epithelial Sodium Proton Exchanger, NHE3. PLOS ONE 2013, 8: e55623. PMID: 23405179, PMCID: PMC3566197, DOI: 10.1371/journal.pone.0055623.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsColonCyclic AMPCytoskeletal ProteinsDogsEpithelial CellsFluorescence Recovery After PhotobleachingHumansMadin Darby Canine Kidney CellsMaleMembrane ProteinsMiceMice, KnockoutMicrofilament ProteinsMicrovilliOctoxynolPhosphorylationProtein TransportRNA, Small InterferingSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsApical actin cytoskeletonNHE3 activitySodium hydrogen exchanger isoform 3CAMP-dependent inhibitionEzrin knockdown miceERM proteinsActin cytoskeletonSodium-proton exchangerApical cytoskeletonApical localizationFunctional regulationWild-type animalsEpithelial cell culture modelEzrinProton exchangersFluorescent recoveryEpithelial phenotypeCytoskeletonMolecular determinantsCell culture modelExchanger isoform 3Functional studiesNon-targeting siRNAApical membraneIsoform 3
2007
Ontogeny of NHE8 in the rat proximal tubule
Becker AM, Zhang J, Goyal S, Dwarakanath V, Aronson PS, Moe OW, Baum M. Ontogeny of NHE8 in the rat proximal tubule. American Journal Of Physiology. Renal Physiology 2007, 293: f255-f261. PMID: 17429030, PMCID: PMC4119019, DOI: 10.1152/ajprenal.00400.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternDNA, ComplementaryElectrophoresis, Polyacrylamide GelFemaleImmunohistochemistryKidney Tubules, ProximalMicroscopy, FluorescenceMicrovilliPregnancyProteinsRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionRNASodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsRat proximal tubuleProximal tubulesAdult ratsNHE3 expressionProximal tubule bicarbonate reabsorptionReal-time RT-PCRProton secretionNeonatal proximal tubuleNHE8 expressionApical membraneBicarbonate reabsorptionMaturational increaseMaturational changesNeonatesNHE8RT-PCRBrush border membrane vesiclesTubulesRatsCortical membrane proteinsSecretionPresent studyDevelopmental expressionAdultsBorder membrane vesiclesNHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity
Kocinsky HS, Dynia DW, Wang T, Aronson PS. NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity. American Journal Of Physiology. Renal Physiology 2007, 293: f212-f218. PMID: 17409282, DOI: 10.1152/ajprenal.00042.2007.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-3-isobutylxanthineAnimalsCells, CulturedColforsinCyclic AMP-Dependent Protein KinasesElectrophoresis, Polyacrylamide GelKidneyKidney Tubules, ProximalMaleMicrovilliParathyroid HormonePhosphodiesterase InhibitorsPhosphorylationRatsRats, Sprague-DawleySerineSodiumSodium RadioisotopesSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersStimulation, ChemicalConceptsSerine 552NHE3 phosphorylationNHE3 activityMicrovillar membrane vesiclesPhosphorylation of NHE3Direct phosphorylationPhosphospecific antibodiesSprague-Dawley ratsExchanger type 3PKA activationMembrane vesiclesSite-specific changesPhosphorylationTransport activityOpossum kidney cellsParathyroid hormoneIntravenous infusionRat modelExchange activityKidney cellsOKP cellsNHE3 inhibitionPKACell modelExact roleMembrane Curvature Alters the Activation Kinetics of the Epithelial Na+/H+ Exchanger, NHE3*
Alexander RT, Malevanets A, Durkan AM, Kocinsky HS, Aronson PS, Orlowski J, Grinstein S. Membrane Curvature Alters the Activation Kinetics of the Epithelial Na+/H+ Exchanger, NHE3*. Journal Of Biological Chemistry 2007, 282: 7376-7384. PMID: 17218318, DOI: 10.1074/jbc.m608557200.Peer-Reviewed Original Research
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 proteinsPDZK1Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites
Kocinsky HS, Girardi AC, Biemesderfer D, Nguyen T, Mentone S, Orlowski J, Aronson PS. Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites. American Journal Of Physiology. Renal Physiology 2005, 289: f249-f258. PMID: 15687252, DOI: 10.1152/ajprenal.00082.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesAntibodies, MonoclonalAntibody SpecificityCell LineChlorocebus aethiopsCOS CellsCyclic AMP-Dependent Protein KinasesDopamineElectrophoresis, Polyacrylamide GelImmunohistochemistryKidneyMaleMiceMice, Inbred BALB CMicroscopy, FluorescenceMicrovilliOpossumsPhosphorylationRatsRats, Sprague-DawleySodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSubcellular FractionsTransfectionConceptsSerine 552Total NHE3Brush border membranePKA consensus sitesEffects of dopamineProximal tubule cellsWestern blot assaysOpossum kidney cellsBaseline phosphorylationPeptide antibodiesInhibition of NHE3Tubule cellsBlot assaysAntibodiesPhosphorylation of NHE3Phosphospecific antibodiesExchanger NHE3NHE3DopamineEndogenous NHE3Kidney cellsVivoPhospho-specific antibodiesTransfection studiesVitro
2004
NHE2‐mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice
Bailey MA, Giebisch G, Abbiati T, Aronson PS, Gawenis LR, Shull GE, Wang T. NHE2‐mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice. The Journal Of Physiology 2004, 561: 765-775. PMID: 15604231, PMCID: PMC1665379, DOI: 10.1113/jphysiol.2004.074716.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAnimalsBicarbonatesBlood PressureGlomerular Filtration RateGuanidinesKidney Tubules, DistalMiceMice, KnockoutPotassiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSulfonesConceptsBicarbonate excretionDistal tubulesBicarbonate reabsorptionNHE3 null miceBicarbonate loadEarly distal tubule fluidNull miceNephron segmentsVivo micropunctureDistal tubule fluidProximal tubule bicarbonate reabsorptionRenal clearance experimentsUrinary bicarbonate excretionGlomerular filtration rateDistal nephron segmentsUrinary bicarbonate lossRat distal tubulesDistal bicarbonate reabsorptionExcretion of bicarbonateMetabolic acidosisFiltration rateVivo microperfusionClearance experimentsReabsorption capacityMicroperfusion experiments
2002
Ion exchangers mediating NaCl transport in the renal proximal tubule
Aronson PS. Ion exchangers mediating NaCl transport in the renal proximal tubule. Cell Biochemistry And Biophysics 2002, 36: 147-153. PMID: 12139400, DOI: 10.1385/cbb:36:2-3:147.Commentaries, Editorials and LettersConceptsProximal tubulesNaCl absorptionOxalate-sulfate exchangeLoop of HenleProximal tubule cellsNaCl transportRenal proximal tubulesRecycling of formateRole of NHE3NHE3 null miceTubule cellsNull micePerfusion solutionNephron segmentsIsoform-specific antibodiesApical membraneRenal brush border vesiclesMammalian proximal tubuleBrush border vesiclesSulfate cotransportBrush border membrane vesiclesTubulesFormate exchangeNHE3Stimulation
2001
Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron
Wang T, Hropot M, Aronson P, Giebisch G. Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. American Journal Of Physiology. Renal Physiology 2001, 281: f1117-f1122. PMID: 11704563, DOI: 10.1152/ajprenal.2001.281.6.f1117.Peer-Reviewed Original ResearchConceptsLoop of HenleHOE 694Proximal tubulesAddition of ethylisopropylamilorideDistal convoluted tubuleBicarbonate reabsorptionConvoluted tubulesSitu microperfusionRat kidneySignificant inhibitionNHE isoformsHenlePredominant isoformTubulesNHE3Functional roleInhibitionNHE2Apical membraneIsoformsApical isoformKidneyMicroperfusionEthylisopropylamilorideNephronAssociation of Na+-H+ Exchanger Isoform NHE3 and Dipeptidyl Peptidase IV in the Renal Proximal Tubule*
Girardi A, Degray B, Nagy T, Biemesderfer D, Aronson P. Association of Na+-H+ Exchanger Isoform NHE3 and Dipeptidyl Peptidase IV in the Renal Proximal Tubule*. Journal Of Biological Chemistry 2001, 276: 46671-46677. PMID: 11590171, DOI: 10.1074/jbc.m106897200.Peer-Reviewed Original ResearchConceptsApical membraneExchanger Isoform NHE3Dipeptidyl peptidase IVN-terminal sequencingProtein complexesDPPIV enzyme activityRenal microvillus membrane vesiclesMicrovillar fractionMembrane populationsMembrane vesiclesPeptidase IVWestern blot analysisMicrovillus membrane vesiclesNHE3 surface expressionBrush borderImmunoelectron microscopyRabbit renal brush borderBlot analysisProteinEnzyme activitySurface expressionMicrovillus membraneNHE3Different poolsImmunoaffinity chromatographyEssential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule
Wang T, Yang C, Abbiati T, Shull G, Giebisch G, Aronson P. Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule. American Journal Of Physiology. Renal Physiology 2001, 281: f288-f292. PMID: 11457720, DOI: 10.1152/ajprenal.2001.281.2.f288.Peer-Reviewed Original ResearchRole of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes
Mennone A, Biemesderfer D, Negoianu D, Yang C, Abbiati T, Schultheis P, Shull G, Aronson P, Boyer J. Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. AJP Gastrointestinal And Liver Physiology 2001, 280: g247-g254. PMID: 11208547, DOI: 10.1152/ajpgi.2001.280.2.g247.Peer-Reviewed Original Research
2000
Active (9.6 S) and Inactive (21 S) Oligomers of NHE3 in Microdomains of the Renal Brush Border*
Biemesderfer D, DeGray B, Aronson P. Active (9.6 S) and Inactive (21 S) Oligomers of NHE3 in Microdomains of the Renal Brush Border*. Journal Of Biological Chemistry 2000, 276: 10161-10167. PMID: 11120742, DOI: 10.1074/jbc.m008098200.Peer-Reviewed Original ResearchAcridine OrangeAnimalsAntibodiesCarrier ProteinsCell MembraneCentrifugation, Density GradientElectrophoresis, Polyacrylamide GelEndosomesFluorescent Antibody Technique, IndirectGoatsHeymann Nephritis Antigenic ComplexHydrogenHydrogen-Ion ConcentrationImmunoblottingImmunohistochemistryKidneyKidney TubulesMagnesiumMaleMembrane GlycoproteinsMicrofilament ProteinsMicroscopy, ElectronMicrovilliMitochondriaPrecipitin TestsProtein BindingProtein Structure, TertiaryRabbitsRatsRats, Sprague-DawleySodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSucroseTime Factors
1999
Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice
Wang T, Yang C, Abbiati T, Schultheis P, Shull G, Giebisch G, Aronson P. Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice. American Journal Of Physiology 1999, 277: f298-f302. PMID: 10444585, DOI: 10.1152/ajprenal.1999.277.2.f298.Peer-Reviewed Original Research
1998
Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger
Schultheis P, Clarke L, Meneton P, Miller M, Soleimani M, Gawenis L, Riddle T, Duffy J, Doetschman T, Wang T, Giebisch G, Aronson P, Lorenz J, Shull G. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nature Genetics 1998, 19: 282-285. PMID: 9662405, DOI: 10.1038/969.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBicarbonatesGene DeletionH(+)-K(+)-Exchanging ATPaseIntestinal AbsorptionIntestinesKidneyMiceMice, KnockoutSodium ChlorideSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsAcid-base balanceAbsorptive defectsNHE3-deficient miceFluid volume homeostasisRenal proximalSlight diarrheaPlasma aldosteroneBlood pressureHomozygous mutant miceExchanger mRNANHE2 isoformsBlood analysisMutant miceCompensatory mechanismsFluid absorptionNHE3 functionVolume homeostasisMiceDistribution of NHE3Cl-/HCO3Channel activityNHE3KidneyATPase mRNAIntestineMembrane Topology of NHE3 EPITOPES WITHIN THE CARBOXYL-TERMINAL HYDROPHILIC DOMAIN ARE EXOPLASMIC*
Biemesderfer D, DeGray B, Aronson P. Membrane Topology of NHE3 EPITOPES WITHIN THE CARBOXYL-TERMINAL HYDROPHILIC DOMAIN ARE EXOPLASMIC*. Journal Of Biological Chemistry 1998, 273: 12391-12396. PMID: 9575193, DOI: 10.1074/jbc.273.20.12391.Peer-Reviewed Original ResearchConceptsExchanger Isoform NHE3Membrane vesiclesAbsence of detergentPlasma membraneBorder membrane vesiclesCarboxyl-terminal hydrophilic domainBrush border membrane vesiclesCarboxyl-terminal domainMembrane topologyCytoskeletal effectorsCarboxyl terminusHigh-resolution immunocytochemistryExoplasmic surfaceCytoplasmic surfaceImmunoprecipitation studiesTransporter activityAmino acidsUltrathin cryosectionsImmunoblot analysisMembrane orientationHydrophilic domainsVesiclesMonoclonal antibodiesIntact microvilliGold technique
1997
Monoclonal antibodies for high-resolution localization of NHE3 in adult and neonatal rat kidney
Biemesderfer D, Rutherford PA, Nagy T, Pizzonia JH, Abu-Alfa AK, Aronson PS. Monoclonal antibodies for high-resolution localization of NHE3 in adult and neonatal rat kidney. American Journal Of Physiology 1997, 273: f289-f299. PMID: 9277590, DOI: 10.1152/ajprenal.1997.273.2.f289.Peer-Reviewed Original ResearchConceptsProximal tubulesRat kidneyMonoclonal antibodiesLoop of HenleHigh-resolution immunocytochemical studiesProximal tubule cellsPrevious immunochemical studiesIsoform-specific monoclonal antibodiesNeonatal rat kidneyTubule cellsImmunocytochemical studyThick limbImmunocytochemical techniquesKidneyLAP cellsRenal epitheliumNHE3Immunochemical studiesHigh-resolution immunocytochemical techniqueAdultsLater stagesNephron development
1996
Role of NHE3 in Mediating Renal Brush Border Na+-H+ Exchange ADAPTATION TO METABOLIC ACIDOSIS*
Wu M, Biemesderfer D, Giebisch G, Aronson P. Role of NHE3 in Mediating Renal Brush Border Na+-H+ Exchange ADAPTATION TO METABOLIC ACIDOSIS*. Journal Of Biological Chemistry 1996, 271: 32749-32752. PMID: 8955109, DOI: 10.1074/jbc.271.51.32749.Peer-Reviewed Original ResearchConceptsMetabolic acidosisControl ratsBrush border membraneRenal brush border vesiclesNHE3 proteinBrush border vesiclesBorder membraneBrush borderNHE3 protein expressionRole of NHE3Western blot analysisNormal ratsAcidosisRatsAcidotic ratsRenal brush border membranePharmacologic inhibitorsProtein expressionExchange activityInhibitor sensitivityNHE3Renal brush borderBlot analysis