2011
Rare mutations in the human Na-K-Cl cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function
Monette MY, Rinehart J, Lifton RP, Forbush B. Rare mutations in the human Na-K-Cl cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function. American Journal Of Physiology. Renal Physiology 2011, 300: f840-f847. PMID: 21209010, PMCID: PMC3074999, DOI: 10.1152/ajprenal.00552.2010.Peer-Reviewed Original ResearchConceptsHEK-293 cellsNa-K-Cl cotransporterTransport functionMajor salt transport pathwayPlasma membrane localizationHEK cellsLow transport activitySequence conservationMembrane localizationProtein functionHeterologous expressionXenopus laevis oocytesImportant residuesMutantsRenal salt reabsorptionMolecular mechanismsIndependent mutationsConstitutive activityTransport activityBlood pressureFunctional consequencesImpaired transport functionSuch mutationsProcessing defectsLaevis oocytes
2008
Exon Loss Accounts for Differential Sorting of Na-K-Cl Cotransporters in Polarized Epithelial Cells
Carmosino M, Giménez I, Caplan M, Forbush B. Exon Loss Accounts for Differential Sorting of Na-K-Cl Cotransporters in Polarized Epithelial Cells. Molecular Biology Of The Cell 2008, 19: 4341-4351. PMID: 18667527, PMCID: PMC2555935, DOI: 10.1091/mbc.e08-05-0478.Peer-Reviewed Original ResearchConceptsDileucine motifNa-K-Cl cotransporterRenal Na-K-Cl cotransporterPolarized epithelial cellsAmino acid stretchApical proteinsApical sortingEvolutionary lossRenal epithelial cell lineGene structurePhylogenetic analysisDifferential sortingDirect traffickingEpithelial cell lineAdditional exonC-terminusMammalian kidneyApical membraneExonsNovel mechanismNKCC2 geneCell linesBasolateral membraneMotifEpithelial cells
2006
The Residues Determining Differences in Ion Affinities among the Alternative Splice Variants F, A, and B of the Mammalian Renal Na-K-Cl Cotransporter (NKCC2)*
Giménez I, Forbush B. The Residues Determining Differences in Ion Affinities among the Alternative Splice Variants F, A, and B of the Mammalian Renal Na-K-Cl Cotransporter (NKCC2)*. Journal Of Biological Chemistry 2006, 282: 6540-6547. PMID: 17186942, DOI: 10.1074/jbc.m610780200.Peer-Reviewed Original ResearchExpression of the basolateral Na–K–Cl cotransporter during mouse nephrogenesis and embryonic development
Heuvel G, Payne J, Igarashi P, Forbush B. Expression of the basolateral Na–K–Cl cotransporter during mouse nephrogenesis and embryonic development. Gene Expression Patterns 2006, 6: 1000-1006. PMID: 16814616, DOI: 10.1016/j.modgep.2006.04.004.Peer-Reviewed Original ResearchConceptsIn situ hybridizationNa-K-Cl cotransporterDorsal root ganglionBranching ureteric budEndocapillary cellsPeripheral nervous systemRoot ganglionTooth budsNasal epitheliumMouse nephrogenesisChoroid plexusSubmandibular glandMature nephronsUreteric budNorthern blot analysisSLC12A2Nervous systemMesenchymal cellsNKCC1Blot analysisMetanephroiNephric structuresGlomeruliMiceEmbryonic development
2004
WNK4 regulates apical and basolateral Cl– flux in extrarenal epithelia
Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B, Aronson PS, Lifton RP. WNK4 regulates apical and basolateral Cl– flux in extrarenal epithelia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 2064-2069. PMID: 14769928, PMCID: PMC357052, DOI: 10.1073/pnas.0308434100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCarrier ProteinsCell PolarityChloridesEpitheliumHumansImmunohistochemistryIon TransportKidneyMembrane ProteinsMembrane Transport ProteinsMiceOocytesProtein Serine-Threonine KinasesRNA, MessengerSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 2Sulfate TransportersXenopus laevisConceptsCl fluxBlood-brain barrierUnrelated ion channelsActivity of mediatorsWNK4 mRNABile ductPancreatic ductExtrarenal expressionExtrarenal tissuesCl(-) handlingPseudohypoaldosteronism type IIChannel ROMKNaCl reabsorptionSerine-threonine kinase WNK4Specialized endotheliumExchanger SLC26A6NaCl cotransporterWNK4 effectsColonic cryptsEpitheliumVariable inhibitionSweat ductsTight junctionsKidneyElectrolyte flux
2002
Spatially Distributed Alternative Splice Variants of the Renal Na-K-Cl Cotransporter Exhibit Dramatically Different Affinities for the Transported Ions*
Giménez I, Isenring P, Forbush B. Spatially Distributed Alternative Splice Variants of the Renal Na-K-Cl Cotransporter Exhibit Dramatically Different Affinities for the Transported Ions*. Journal Of Biological Chemistry 2002, 277: 8767-8770. PMID: 11815599, DOI: 10.1074/jbc.c200021200.Peer-Reviewed Original Research
2000
Basolateral K-Cl Cotransporter Regulates Colonic Potassium Absorption in Potassium Depletion*
Sangan P, Brill S, Sangan S, Forbush B, Binder H. Basolateral K-Cl Cotransporter Regulates Colonic Potassium Absorption in Potassium Depletion*. Journal Of Biological Chemistry 2000, 275: 30813-30816. PMID: 10878016, DOI: 10.1074/jbc.m003931200.Peer-Reviewed Original ResearchConceptsK-Cl cotransporterMembrane HK-Cl cotransportActive potassium absorptionProtein expressionBasolateral membranePotassium absorptionK-ATPaseNorthern blot analysisKCC1 mRNACoordinated regulationAlpha-subunit mRNABeta-subunit mRNAMRNA abundanceBlot analysisMRNAExpressionProteinMembraneCotransporterDepletionRat distal colonCDNAKCC1
1998
Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding
Isenring P, Jacoby S, Chang J, Forbush B. Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding. The Journal Of General Physiology 1998, 112: 549-558. PMID: 9806964, PMCID: PMC2229443, DOI: 10.1085/jgp.112.5.549.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBumetanideCarrier ProteinsCells, CulturedChloridesDiureticsHumansKidneyKineticsMutagenesis, Site-DirectedOligonucleotide ProbesPotassiumProtein Structure, TertiaryRecombinant Fusion ProteinsRubidium RadioisotopesSharksSodiumSodium-Potassium-Chloride SymportersSpecies Specificity
1996
Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human A NEW MEMBER OF THE CATION-CHLORIDE COTRANSPORTER FAMILY*
Gillen C, Brill S, Payne J, Forbush B. Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human A NEW MEMBER OF THE CATION-CHLORIDE COTRANSPORTER FAMILY*. Journal Of Biological Chemistry 1996, 271: 16237-16244. PMID: 8663127, DOI: 10.1074/jbc.271.27.16237.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCarrier ProteinsCell LineChloridesCloning, MolecularDatabases, FactualDNA PrimersDNA, ComplementaryHumansKidneyKineticsModels, StructuralMolecular Sequence DataMultigene FamilyOpen Reading FramesPhylogenyPolymerase Chain ReactionPotassiumProtein Structure, SecondaryRabbitsRatsRecombinant ProteinsRubidiumSequence Homology, Amino AcidSequence Tagged SitesSymportersTransfectionConceptsNa-K-Cl cotransporterK-Cl cotransportK-ClRat brain cDNA libraryThiazide-sensitive Na-Cl cotransporterRate of 86Rb effluxBrain cDNA libraryBumetanide-sensitive Na-K-Cl cotransporterN-linked glycosylation sitesC-terminal regionSubstantial sequence homologyNa-Cl cotransporterNa-K-ClHEK 293) cellsUptake of 86RbNorthern blot analysisGenome sequenceCDNA libraryHydropathy analysisFunctional expressionSequence homologyReverse transcription-polymerase chain reactionHuman embryonic kidneySequence analysisHomologous cDNA probesImmunocytochemical studies of the Na-K-Cl cotransporter of shark kidney
Biemesderfer D, Payne J, Lytle C, Forbush B. Immunocytochemical studies of the Na-K-Cl cotransporter of shark kidney. American Journal Of Physiology 1996, 270: f927-f936. PMID: 8764311, DOI: 10.1152/ajprenal.1996.270.6.f927.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-ClBasolateral membraneCotransporter proteinBasolateral membranes of proximal tubulesNa-K-Cl cotransport proteinShark kidneyBasolateral plasma membraneDistal tubule segmentsApical plasma membraneShark rectal glandDistal nephronReabsorptive epitheliaNaCl reabsorptionPlasma membraneWestern blot analysisTubule segmentsProximal tubulesDiluting segmentWeak stainingShark Squalus acanthiasPresence of multiple isoformsDogfish shark Squalus acanthiasCotransporterMonoclonal antibodies
1995
Localization of the renal Na−K−Cl cotransporter gene (Slc 12a1) on mouse Chromosome 2
Quaggin S, Payne J, Forbush B, Igarashi P. Localization of the renal Na−K−Cl cotransporter gene (Slc 12a1) on mouse Chromosome 2. Mammalian Genome 1995, 6: 557-558. PMID: 8589530, DOI: 10.1007/bf00356178.Peer-Reviewed Original Research
1994
Alternatively spliced isoforms of the putative renal Na-K-Cl cotransporter are differentially distributed within the rabbit kidney.
Payne J, Forbush B. Alternatively spliced isoforms of the putative renal Na-K-Cl cotransporter are differentially distributed within the rabbit kidney. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 4544-4548. PMID: 7514306, PMCID: PMC43822, DOI: 10.1073/pnas.91.10.4544.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsBase SequenceBlotting, NorthernCarrier ProteinsCloning, MolecularColonConserved SequenceDogfishGene LibraryHumansKidneyKidney CortexKidney MedullaMembrane ProteinsMolecular Sequence DataOpen Reading FramesPoly ARabbitsRNARNA, MessengerSalt GlandSequence Homology, Amino AcidSodium-Potassium-Chloride SymportersTranscription, GeneticConceptsNa-K-Cl cotransporterNorthern blot analysisRabbit kidney cDNA libraryRenal Na-K-Cl cotransporterC-terminal cytoplasmic domainC-terminal cytoplasmic regionConsensus splice acceptor siteKidney cDNA libraryAmino acid hydropathySplice acceptor siteBlot analysisN-linked glycosylationRegions of divergenceIntronic DNACDNA clonesCassette exonsCDNA libraryProtein kinase ACytoplasmic domainSpliced isoformsTransmembrane helicesCDNA probeCytoplasmic regionHomologous variantMultiple clonesKinetic heterogeneity of phosphoenzyme of Na,K-ATPase modeled by unmixed lipid phases. Competence of the phosphointermediate.
Klodos I, Post R, Forbush B. Kinetic heterogeneity of phosphoenzyme of Na,K-ATPase modeled by unmixed lipid phases. Competence of the phosphointermediate. Journal Of Biological Chemistry 1994, 269: 1734-1743. PMID: 8294422, DOI: 10.1016/s0021-9258(17)42089-8.Peer-Reviewed Original Research
1991
[3H]bumetanide binding to mouse kidney membranes: identification of corresponding membrane proteins
Haas M, Dunham P, Forbush B. [3H]bumetanide binding to mouse kidney membranes: identification of corresponding membrane proteins. American Journal Of Physiology 1991, 260: c791-c804. PMID: 2018111, DOI: 10.1152/ajpcell.1991.260.4.c791.Peer-Reviewed Original ResearchMeSH KeywordsAffinity LabelsAnimalsBenzophenonesBumetanideCarcinoma, Ehrlich TumorCarrier ProteinsCell FractionationCell MembraneCentrifugation, Density GradientFemaleKidneyKidney CortexKidney MedullaKineticsMembrane ProteinsMiceProtein BindingSodium-Potassium-Chloride SymportersSulfanilamidesTritiumConceptsMouse kidney membranesKidney membranesNa-K-Cl cotransport systemNa-K-ClLow-affinity peakDog kidney membraneMouse Ehrlich ascites tumor cellsMouse kidney proteinsDog kidneyCrude plasma membranesTumor cellsWestern blot analysisEhrlich ascites tumor cellsCotransport systemAscites tumor cellsMouse kidneyMiceStaining profileLow-affinity sitesWestern blottingBinding sitesAntiserum cross-reactedKidneyBlot analysisKidney proteins
1990
Biosynthesis of the Na,K-ATPase in Madin-Darby canine kidney cells. Activation and cell surface delivery.
Caplan MJ, Forbush B, Palade GE, Jamieson JD. Biosynthesis of the Na,K-ATPase in Madin-Darby canine kidney cells. Activation and cell surface delivery. Journal Of Biological Chemistry 1990, 265: 3528-3534. PMID: 2154482, DOI: 10.1016/s0021-9258(19)39801-1.Peer-Reviewed Original Research
1988
Rapid 86Rb release from an occluded state of the Na,K-pump reflects the rate of dephosphorylation or dearsenylation.
Forbush B. Rapid 86Rb release from an occluded state of the Na,K-pump reflects the rate of dephosphorylation or dearsenylation. Journal Of Biological Chemistry 1988, 263: 7961-7969. PMID: 2836403, DOI: 10.1016/s0021-9258(18)68428-5.Peer-Reviewed Original ResearchRapid release of 45Ca from an occluded state of the Na,K-pump.
Forbush B. Rapid release of 45Ca from an occluded state of the Na,K-pump. Journal Of Biological Chemistry 1988, 263: 7970-7978. PMID: 2836404, DOI: 10.1016/s0021-9258(18)68429-7.Peer-Reviewed Original ResearchConceptsNa,K-pumpNa,K-ATPaseK-pumpK-ATPasePhosphorylation of Na,K-ATPaseRelease of 45CaExposure to K+Release of 86RbApparent affinityCa2+Transport sitesK+ congenerMg2+ + ATPIntracellular faceRelease of K+Simultaneous occlusionExtracellular sitesPrevent phosphorylationCa2Exposure to Mg2Extracellular faceReleaseAbsence of PiN-methylglucamineIntracellular mediumThe interaction of amines with the occluded state of the Na,K-pump.
Forbush B. The interaction of amines with the occluded state of the Na,K-pump. Journal Of Biological Chemistry 1988, 263: 7979-7988. PMID: 2836405, DOI: 10.1016/s0021-9258(18)68430-3.Peer-Reviewed Original ResearchConceptsRelease of 86RbInteraction of aminesPresence of aminesNa,K-pumpIntracellular faceDog kidney NaK-pumpK-ATPaseEffect of aminesBenzyl amineBifunctional aminesBlock releaseKidney NaOcclusionOrganic cationsPre-incubationAminesAmine blocksTransport sitesPresence of ATPK+ siteCompetitive mannerLow affinityOccluded statePhotoaffinity labelling of a 150 kDa (Na + K + Cl)-cotransport protein from duck red cells with an analog of bumetanide
Haas M, Forbush B. Photoaffinity labelling of a 150 kDa (Na + K + Cl)-cotransport protein from duck red cells with an analog of bumetanide. Biochimica Et Biophysica Acta 1988, 939: 131-144. PMID: 3349075, DOI: 10.1016/0005-2736(88)90054-5.Peer-Reviewed Original ResearchConceptsDuck red cellsRed cellsSimultaneous presence of Na+Binding to intact cellsIncubation mediumDog kidney membraneConsistent with labelingDuck red blood cellsRed blood cellsBumetanideCotransporterRed cell membraneBlood cellsKidney membranesPresence of Na+DucksCellsCell membranePlasma membraneSDS-polyacrylamide gelsIntact cellsSDS-polyacrylamideProteinNorepinephrine
1987
Na,K,Cl-cotransport system: characterization by bumetanide binding and photolabelling.
Haas M, Forbush B. Na,K,Cl-cotransport system: characterization by bumetanide binding and photolabelling. Kidney International Supplement 1987, 23: s134-43. PMID: 3481640.Peer-Reviewed Original Research