2005
Control of the CFTR channel's gates.
Vergani P, Basso C, Mense M, Nairn A, Gadsby D. Control of the CFTR channel's gates. Biochemical Society Transactions 2005, 33: 1003-7. PMID: 16246032, PMCID: PMC2728124, DOI: 10.1042/bst20051003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid SequenceATP-Binding Cassette TransportersBinding SitesCystic Fibrosis Transmembrane Conductance RegulatorHumansIon Channel GatingMutagenesisNucleotidesConceptsChannel gateIon channelsProtein family membersNBD dimer interfaceAnion-selective poreEvolutionary conservationABC proteinsCFTR moleculesForm homodimersTransmembrane domainATP bindingHeterodimer interfaceDimer interfaceMolecular mechanismsTight dimerizationNBDATPSingle-channel recordingsResiduesFamily membersNBD1NBD2Cystic fibrosis patientsMutagenesisHomodimer
2000
Severed Channels Probe Regulation of Gating of Cystic Fibrosis Transmembrane Conductance Regulator by Its Cytoplasmic Domains
Csanády L, Chan K, Seto-Young D, Kopsco D, Nairn A, Gadsby D. Severed Channels Probe Regulation of Gating of Cystic Fibrosis Transmembrane Conductance Regulator by Its Cytoplasmic Domains. The Journal Of General Physiology 2000, 116: 477-500. PMID: 10962022, PMCID: PMC2233695, DOI: 10.1085/jgp.116.3.477.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdenylyl ImidodiphosphateAnimalsBase SequenceCyclic AMP-Dependent Protein KinasesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA PrimersFemaleHumansIn Vitro TechniquesIon Channel GatingModels, BiologicalMutationOocytesPhosphorylationProtein Structure, TertiaryRecombinant ProteinsXenopusConceptsR domainCFTR channelsPhosphorylated R domainWild-type CFTR channelsCytoplasmic regulatory domainCystic fibrosis transmembrane conductance regulatorNucleotide Binding DomainFibrosis transmembrane conductance regulatorDetailed functional characteristicsWT channelsApparent ATP affinityTransmembrane conductance regulatorCFTR Cl- channelPresence of PKANonhydrolyzable ATP analogue AMPPNPATP analogue AMPPNPATP bindingRegulatory domainCytoplasmic domainWt-CFTRBinding domainsGating eventsConductance regulatorATP affinityFunctional interactionSevered Molecules Functionally Define the Boundaries of the Cystic Fibrosis Transmembrane Conductance Regulator's Nh2-Terminal Nucleotide Binding Domain
Chan K, Csanády L, Seto-Young D, Nairn A, Gadsby D. Severed Molecules Functionally Define the Boundaries of the Cystic Fibrosis Transmembrane Conductance Regulator's Nh2-Terminal Nucleotide Binding Domain. The Journal Of General Physiology 2000, 116: 163-180. PMID: 10919864, PMCID: PMC2229491, DOI: 10.1085/jgp.116.2.163.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine MonophosphateAnimalsCystic Fibrosis Transmembrane Conductance RegulatorEndoplasmic ReticulumEpitopesFemaleGene DeletionGene ExpressionIon Channel GatingKineticsMembrane PotentialsMolecular Sequence DataMutagenesisOligopeptidesOocytesPatch-Clamp TechniquesPeptide FragmentsPeptidesPrecipitin TestsProtein BindingProtein Structure, TertiarySequence Homology, Amino AcidTransfectionXenopus laevisConceptsR domainCFTR channelsCOOH terminusMature formFull-length CFTRCystic fibrosis transmembrane conductance regulatorAmino acids 590Nucleotide Binding DomainFibrosis transmembrane conductance regulatorExcised patch recordingsChannel activityFamily of ATPRequirement of phosphorylationCFTR channel activityTransmembrane conductance regulatorNBD1 domainSmaller single-channel conductanceCFTR polypeptideTransmembrane domainATP bindingRegulatory domainCassette proteinNBD structuresNBD1Binding domains
1999
Regulation of CFTR Cl- ion channels by phosphorylation and dephosphorylation.
Gadsby D, Nairn A. Regulation of CFTR Cl- ion channels by phosphorylation and dephosphorylation. Advances In Second Messenger And Phosphoprotein Research 1999, 33: 79-106. PMID: 10218115, DOI: 10.1016/s1040-7952(99)80006-8.Peer-Reviewed Original ResearchAdenosine TriphosphateBinding SitesCalcium-Calmodulin-Dependent Protein KinasesCyclic AMP-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansIon Channel GatingModels, MolecularPhosphoprotein PhosphatasesPhosphorylationProtein Kinase CControl of CFTR Channel Gating by Phosphorylation and Nucleotide Hydrolysis
GADSBY D, NAIRN A. Control of CFTR Channel Gating by Phosphorylation and Nucleotide Hydrolysis. Physiological Reviews 1999, 79: s77-s107. PMID: 9922377, DOI: 10.1152/physrev.1999.79.1.s77.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCystic Fibrosis Transmembrane Conductance RegulatorHumansHydrolysisIon Channel GatingModels, BiologicalNucleotidesPhosphoprotein PhosphatasesPhosphorylationProtein KinasesConceptsNucleotide-binding domainCFTR channelsCytoplasmic nucleotide-binding domainsNucleotide hydrolysisChannel gatingDependent phosphorylation eventsCystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channelCFTR channel currentsCFTR channel gatingATP moleculesLarge cytoplasmic domainCommon lethal genetic diseaseSecond ATP moleculeSingle CFTR channelsATP hydrolysis cycleLethal genetic diseasePhosphorylation eventsGating cycleRegulatory domainCytoplasmic domainDifferent phosphoformsProgressive phosphorylationMultiple proteinsProtein productsHydrolysis cycle
1998
ATP hydrolysis cycles and the gating of CFTR Cl- channels.
Gadsby D, Dousmanis A, Nairn A. ATP hydrolysis cycles and the gating of CFTR Cl- channels. Acta Physiologica Scandinavica. Supplementum 1998, 643: 247-56. PMID: 9789567.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdenylyl ImidodiphosphateAnimalsCystic Fibrosis Transmembrane Conductance RegulatorGuinea PigsHydrolysisIon Channel GatingMagnesiumProtein ConformationConceptsC-terminal nucleotideCFTR channelsAMP-PNPG proteinsN-terminal nucleotideCentral regulatory domainMore serine residuesProtein kinase ACFTR Cl- channelHydrolysis of ATPATP hydrolysis cycleCl- channelsGating cycleRegulatory domainCytoplasmic domainTight bindingSerine residuesHydrolyse ATPSecond ATPSequence homologyTransport proteinsKinase AOpen conformationAnalogues of ATPFunctional similarityCellular Localization of Calmodulin-dependent Protein Kinases I and II to A-cells and D-cells of the Endocrine Pancreas
Matovcik L, Nairn A, Gorelick F. Cellular Localization of Calmodulin-dependent Protein Kinases I and II to A-cells and D-cells of the Endocrine Pancreas. Journal Of Histochemistry & Cytochemistry 1998, 46: 519-526. PMID: 9524198, DOI: 10.1177/002215549804600412.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 1Calcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinCystic Fibrosis Transmembrane Conductance RegulatorDigestive SystemFluorescent Antibody Technique, IndirectGlucagonImmunoblottingIslets of LangerhansMicroscopy, ConfocalPancreasRatsSomatostatinSomatostatin-Secreting CellsTissue DistributionConceptsCaM kinase IKinase IProtein kinase ICaM kinase IIGlucagon secretionKinase IICalmodulin-dependent protein kinase ISomatostatin cellsDependent protein kinase IA cellsSomatostatin-containing D-cellsD cellsDifferent cell typesRegulation of Ca2Islets of LangerhansCaM kinaseCytosolic proteinsI antibodiesSomatostatin granulesPancreatic polypeptideCellular localizationRegulatory rolePeptide antibodiesIntracellular Ca2Endocrine pancreasActions of Genistein on Cystic Fibrosis Transmembrane Conductance Regulator Channel Gating
Wang F, Zeltwanger S, Yang I, Nairn A, Hwang T. Actions of Genistein on Cystic Fibrosis Transmembrane Conductance Regulator Channel Gating. The Journal Of General Physiology 1998, 111: 477-490. PMID: 9482713, PMCID: PMC2217116, DOI: 10.1085/jgp.111.3.477.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBinding SitesCells, CulturedCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEnzyme InhibitorsGenisteinIn Vitro TechniquesInsectaIon Channel GatingIon ChannelsKineticsMembrane PotentialsPhosphorylationConceptsCystic Fibrosis Transmembrane Conductance Regulator Channel GatingCFTR channelsSerine/threonine proteinTyrosine kinaseCystic fibrosis transmembrane conductance regulator (CFTR) channel activityDirect bindingHi-5 insect cellsCFTR channel currentsTyrosine phosphatase inhibitorMicroM genisteinProtein kinase AEffects of genisteinNonhydrolyzable ATP analogRecombinant CFTRProtein phosphatasePossible molecular mechanismsCFTR gatingInsect cellsPhosphatase inhibitorCalyculin ACFTR proteinAbsence of genisteinATP hydrolysisKinase ANIH3T3 cells
1995
Isotype-specific Activation of Cystic Fibrosis Transmembrane Conductance Regulator-Chloride Channels by cGMP-dependent Protein Kinase II (∗)
French P, Bijman J, Edixhoven M, Vaandrager A, Scholte B, Lohmann S, Nairn A, de Jonge H. Isotype-specific Activation of Cystic Fibrosis Transmembrane Conductance Regulator-Chloride Channels by cGMP-dependent Protein Kinase II (∗). Journal Of Biological Chemistry 1995, 270: 26626-26631. PMID: 7592887, DOI: 10.1074/jbc.270.44.26626.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCattleCell LineCell MembraneChloride ChannelsCyclic GMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorEnzyme InhibitorsIntestinesIsoenzymesKineticsLungMacromolecular SubstancesMarine ToxinsMembrane PotentialsMicrovilliOxazolesPeptide FragmentsPhosphopeptidesPhosphorylationProtein Phosphatase 1Protein Tyrosine PhosphatasesRatsRecombinant ProteinsSwineTransfectionConceptsProtein kinaseType II cGMP-dependent protein kinaseCGMP-dependent protein kinase IICAMP-dependent protein kinaseCystic fibrosis transmembrane conductance regulator (CFTR) chloride channelCGMP-dependent protein kinaseCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorProtein kinase IINIH 3T3 fibroblastsRat intestinal cell lineRecombinant CFTRCF 2Presence of cGMPProtein phosphatasePresence of ATPCAK activationPhosphatase 1Phosphopeptide mapsCatalytic subunitCalyculin ACatalytic fragmentKinase IIConductance regulatorCystic Fibrosis Transmembrane Conductance Regulator Is Found Within Brain Ventricular Epithelium and Choroid Plexus
Hincke M, Nairn A, Staines W. Cystic Fibrosis Transmembrane Conductance Regulator Is Found Within Brain Ventricular Epithelium and Choroid Plexus. Journal Of Neurochemistry 1995, 64: 1662-1668. PMID: 7534334, DOI: 10.1046/j.1471-4159.1995.64041662.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCerebral VentriclesChoroid PlexusCystic Fibrosis Transmembrane Conductance RegulatorEpendymaImmunohistochemistryMaleMembrane ProteinsRatsRats, WistarTissue DistributionConceptsCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorConductance regulatorCystic fibrosis gene productBrain Ventricular EpitheliumCyclic AMP-dependent phosphorylationGene productsCFTR proteinFine punctaChloride transportersCl- channelsCyclic AMP-elevating agentsEpendymal functionWestern blottingRegulatorVentricular epitheliumPhosphorylationChoroid plexusProteinTransportersRodent brainPunctaRegulationMicrodissection
1994
Regulation of CFTR channel gating
Gadsby D, Nairn A. Regulation of CFTR channel gating. Trends In Biochemical Sciences 1994, 19: 513-518. PMID: 7531880, DOI: 10.1016/0968-0004(94)90141-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChloride ChannelsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansIon Channel GatingMembrane ProteinsConceptsChannel gatingCystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channelAMP-dependent protein kinaseCFTR channel gatingReceptor-mediated activationRegulatory domainProtein kinaseATP hydrolysisCFTR channelsCl- channelsEpithelial cellsChannel openingComplex mechanismsCellsRecent advancesKinaseGenesPhosphorylationSerineGatingCFTRMutationsRegulationStemActivationSubcellular localization of CFTR to endosomes in a ductal epithelium
Webster P, Vanacore L, Nairn A, Marino C. Subcellular localization of CFTR to endosomes in a ductal epithelium. American Journal Of Physiology 1994, 267: c340-c348. PMID: 7521124, DOI: 10.1152/ajpcell.1994.267.2.c340.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEndocytosisEpitheliumFluorescent Antibody TechniqueImmunohistochemistryMaleMembrane ProteinsMicroscopy, FluorescenceOrganellesRatsRats, Sprague-DawleyReceptors, Cell SurfaceSubcellular FractionsSubmandibular GlandTissue DistributionConceptsCystic fibrosis transmembrane conductance regulatorPlasma membraneFibrosis transmembrane conductance regulatorApical plasma membraneAnti-CFTR antibodiesNormal epithelial cell populationsTransmembrane conductance regulatorCytochemical evidenceReceptor-mediated endocytosisCFTR moleculesEpithelial cell populationsCellular processesSubcellular compartmentsSubcellular localizationEarly endosomesMembrane recyclingConductance regulatorSubcellular distributionSubapical vesiclesApical poleEndosomesCFTR functionImmunoelectron microscopyCell populationsCFTR immunoreactivityRegulation of the gating of cystic fibrosis transmembrane conductance regulator C1 channels by phosphorylation and ATP hydrolysis.
Hwang T, Nagel G, Nairn A, Gadsby D. Regulation of the gating of cystic fibrosis transmembrane conductance regulator C1 channels by phosphorylation and ATP hydrolysis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 4698-4702. PMID: 7515176, PMCID: PMC43855, DOI: 10.1073/pnas.91.11.4698.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdenylyl ImidodiphosphateAnimalsCells, CulturedChloride ChannelsCyclic AMP-Dependent Protein KinasesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorElectric ConductivityGuinea PigsIon Channel GatingMembrane ProteinsPhosphorylationConceptsCFTR channelsATP hydrolysisPresence of ATPDomains of CFTRCystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channelProtein kinase AATP analogue 5'Kinase AOpen probabilityAMP-PNPPhosphorylationLow open probabilityCl- channelsATPATP actionIntact cardiac myocytesNucleotidesCFTRSecond siteExcised patchesHigh open probabilityCardiac myocytesChannel closingC1 channelsAnalogue 5Coupling of CFTR Cl− channel gating to an ATP hydrolysis cycle
Baukrowitz T, Hwang T, Nairn A, Gadsby D. Coupling of CFTR Cl− channel gating to an ATP hydrolysis cycle. Neuron 1994, 12: 473-482. PMID: 7512348, DOI: 10.1016/0896-6273(94)90206-2.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBerylliumChloride ChannelsCystic Fibrosis Transmembrane Conductance RegulatorFemaleFluoridesGuinea PigsHydrolysisIon Channel GatingMaleMembrane ProteinsMyocardiumSarcolemmaVanadatesConceptsCystic fibrosis transmembrane conductance regulatorATP hydrolysis cycleHydrolysis cycleCFTR channelsFibrosis transmembrane conductance regulatorProtein kinase ATransmembrane conductance regulatorATP hydrolysisKinase AConductance regulatorNucleoside triphosphatesChannel openingInorganic phosphate analogueATPPhosphate analogueCardiac myocytesInorganic phosphateMean open timeRegulatorHydrolysis productsBeF3Open timeCycleTriphosphate
1993
Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells
Cohn J, Strong T, Picciotto M, Nairn A, Collins F, Fitz J. Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology 1993, 105: 1857-1864. PMID: 7504645, DOI: 10.1016/0016-5085(93)91085-v.Peer-Reviewed Original ResearchMeSH KeywordsAntiportersBile DuctsChloride ChannelsChloride-Bicarbonate AntiportersCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpitheliumHumansMembrane ProteinsRNA, Messenger
1992
The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator
Nagel G, Hwang T, Nastiuk K, Nairn A, Gadsbyt D. The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator. Nature 1992, 360: 81-84. PMID: 1279437, DOI: 10.1038/360081a0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBiological Transport, ActiveBlotting, NorthernChloride ChannelsChlorineCystic Fibrosis Transmembrane Conductance RegulatorGuanosine TriphosphateGuinea PigsIn Vitro TechniquesIon Channel GatingMembrane PotentialsMembrane ProteinsMyocardiumPhosphorylationProtein KinasesReceptors, Adrenergic, betaRNAConceptsCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorConductance regulatorCyclic AMP-dependent protein kinaseAMP-dependent protein kinasePKA catalytic subunitResult of phosphorylationPhosphorylated channelsCatalytic subunitProtein kinaseSingle-channel conductanceNucleoside triphosphatesPhosphorylationMembrane potentialEpithelial cellsChannel activationRegulatorChannel conductanceCystic fibrosisKinaseCardiac ventricular myocytesSubunitsProteinUnitary current amplitudeCharacterization of the cystic fibrosis transmembrane conductance regulator in a colonocyte cell line.
Cohn J, Nairn A, Marino C, Melhus O, Kole J. Characterization of the cystic fibrosis transmembrane conductance regulator in a colonocyte cell line. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 2340-2344. PMID: 1372442, PMCID: PMC48653, DOI: 10.1073/pnas.89.6.2340.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell LineColonCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorFluorescent Antibody TechniqueHumansImmunoblottingImmunoenzyme TechniquesImmunohistochemistryMembrane ProteinsMolecular Sequence DataPeptide MappingPeptidesPhosphopeptidesConceptsCystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorConductance regulatorTwo-dimensional phosphopeptide mappingT84 cellsProtein kinase ACell linesProtein kinase CSDS/PAGEPhosphopeptide mappingPhosphorylation sitesProminent substrateCFTR peptidesEquivalent proteinsKinase ASame proteinKinase CTerminal sequenceCell lysatesN-glycanaseProteinAnti-peptide antibodiesImmunoblot signalsCFTR immunoreactivity
1991
Identification and localization of a dogfish homolog of human cystic fibrosis transmembrane conductance regulator.
Marshall J, Martin K, Picciotto M, Hockfield S, Nairn A, Kaczmarek L. Identification and localization of a dogfish homolog of human cystic fibrosis transmembrane conductance regulator. Journal Of Biological Chemistry 1991, 266: 22749-22754. PMID: 1718999, DOI: 10.1016/s0021-9258(18)54631-7.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCell MembraneCloning, MolecularCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNADogfishHumansImmunoenzyme TechniquesMembrane ProteinsMolecular Sequence DataMolecular WeightProtein KinasesRectumSebaceous GlandsSequence Homology, Nucleic AcidSubstrate SpecificityConceptsCystic fibrosis transmembrane conductance regulatorHuman cystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorDogfish proteinRectal glandConductance regulatorPutative substrate sitesCyclic AMP-dependent protein kinaseAMP-dependent protein kinaseMajor phosphorylation siteCyclic AMP-dependent protein phosphorylationApical plasma membraneAmino acid sequenceStudy of regulationPhosphorylation sitesProtein phosphorylationCDNA clonesProtein kinaseSimilar molecular massCFTR sequencePlasma membraneAcid sequenceImmunolocalization studiesMolecular mass