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 ResearchConceptsChannel 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 ResearchConceptsNucleotide-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 ResearchConceptsC-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 similarityActions 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 ResearchConceptsCystic 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
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 advancesKinaseGenesPhosphorylationSerineGatingCFTRMutationsRegulationStemActivationRegulation 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 ResearchConceptsCFTR 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 ResearchConceptsCystic 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 timeCycleTriphosphateRegulation of CFTR channel gating.
Gadsby D, Hwang T, Baukrowitz T, Nagel G, Horie M, Nairn A. Regulation of CFTR channel gating. The Journal Of Physiological Sciences 1994, 44 Suppl 2: s183-92. PMID: 7752525.Peer-Reviewed Original ResearchConceptsNon-hydrolyzable ATP analog AMP-PNPCystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channelAMP-PNPCFTR channel gatingProtein kinase A (PKA) phosphorylationATP analogue AMP-PNPAnalogue AMP-PNPCFTR's twoA PhosphorylationATP hydrolysisChannel gatingCl- channelsChannel openingNBDRegulationMultiple sitesPhosphorylationCFTROrthovanadateATPGatingDomain
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 amplitudecGMP-dependent protein kinase regulation of a chloride channel in T84 cells
Lin M, Nairn A, Guggino S. cGMP-dependent protein kinase regulation of a chloride channel in T84 cells. American Journal Of Physiology 1992, 262: c1304-c1312. PMID: 1317106, DOI: 10.1152/ajpcell.1992.262.5.c1304.Peer-Reviewed Original ResearchConceptsProtein kinaseChloride channelsIntestinal epithelial cellsCGMP-dependent protein kinaseProtein kinase regulationApical membraneDependent protein kinaseT84 cellsEpithelial cellsInhibitor of PKGKinase regulationCatalytic subunitCombination of ATPNonhydrolyzable formExcessive fluid secretionIntracellular faceEscherichia coliElevated guanosineSingle-channel recordingsATPKinasePKGLinear current-voltage relationshipCellsChloride secretion
1991
Enhancement of the Glutamate Response by cAMP-Dependent Protein Kinase in Hippocampal Neurons
Greengard P, Jen J, Nairn A, Stevens C. Enhancement of the Glutamate Response by cAMP-Dependent Protein Kinase in Hippocampal Neurons. Science 1991, 253: 1135-1138. PMID: 1716001, DOI: 10.1126/science.1716001.Peer-Reviewed Original ResearchConceptsProtein kinaseCAMP-dependent protein kinaseGlutamate receptor channelsMonophosphate-dependent protein kinaseReceptor channelsType glutamate receptor channelsAdenylate cyclase cascadeCultured hippocampal pyramidal neuronsSpontaneous excitatory postsynaptic currentsWhole-cell current responsesSingle-channel analysisNeuromodulatory regulationMammalian brainExcitatory postsynaptic currentsHippocampal pyramidal neuronsKinaseLong-term potentiationPyramidal neuronsPostsynaptic currentsGlutamate responseExcitatory neurotransmitterMean open timeHippocampal neuronsAdenylate cyclaseSynaptic events