2020
Cumulative hydropathic topology of a voltage‐gated sodium channel at atomic resolution
Xenakis M, Kapetis D, Yang Y, Heijman J, Waxman S, Lauria G, Faber C, Smeets H, Westra R, Lindsey P. Cumulative hydropathic topology of a voltage‐gated sodium channel at atomic resolution. Proteins Structure Function And Bioinformatics 2020, 88: 1319-1328. PMID: 32447794, DOI: 10.1002/prot.25951.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceArcobacterBacterial ProteinsBinding SitesHydrophobic and Hydrophilic InteractionsIon Channel GatingModels, MolecularProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsSodiumThermodynamicsVoltage-Gated Sodium ChannelsConceptsVoltage-gated sodium channelsBacterial channelsPhysiological cellular activitySodium channelsCellular activitiesCell membraneBiological poresPore stabilityAtomic resolutionBiophysical significanceMembrane surfaceHydropathicityGenesProteinMutationsWide spectrumMembraneFunctional architectureAccumulationComputational frameworkSodium ionsPores
2018
Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner
Li Y, Zhu T, Yang H, Dib-Hajj S, Waxman S, Yu Y, Xu TL, Cheng X. Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. Molecular Pain 2018, 14: 1744806918782229. PMID: 29790812, PMCID: PMC6024516, DOI: 10.1177/1744806918782229.Peer-Reviewed Original ResearchConceptsND7/23 cellsDRG neuron excitabilityModulation of Nav1.7New pain therapeuticsVoltage-gated sodium channel Nav1.7Fyn kinaseWhole-cell recordingsSodium channel Nav1.7Elevated protein expressionCell type-specific modulationHuman embryonic kidney 293 cellsTyrosine kinasePain disordersEmbryonic kidney 293 cellsPain therapeuticsNeuron excitabilityPain perceptionMutant channelsChannel Nav1.7Kidney 293 cellsNav1.7HEK-293 cellsNav1.7 channelsCell type-dependent mannerType-dependent manner
2015
De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy
Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans M, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels R, Meisler MH, Kamsteeg EJ. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. Journal Of Medical Genetics 2015, 52: 330. PMID: 25725044, PMCID: PMC4413743, DOI: 10.1136/jmedgenet-2014-102813.Peer-Reviewed Original ResearchConceptsClinical exome sequencingClinical featuresEarly-infantile epileptic encephalopathy type 13Intellectual disabilityVoltage-gated sodium channel Nav1.6De novo SCN8A mutationFunction mutationsExome sequencingSodium channel Nav1.6Variable clinical featuresGenotype-phenotype correlationSCN8A mutationsChannel Nav1.6Hyperpolarising shiftMutant sodium channelsPatientsDe novoHeterozygous lossSodium channelsElectrophysiological analysisClinical interpretationType 13DisabilitySeizuresWildtype channel
2013
A new Nav1.7 mutation in an erythromelalgia patient
Estacion M, Yang Y, Dib-Hajj SD, Tyrrell L, Lin Z, Yang Y, Waxman SG. A new Nav1.7 mutation in an erythromelalgia patient. Biochemical And Biophysical Research Communications 2013, 432: 99-104. PMID: 23376079, DOI: 10.1016/j.bbrc.2013.01.079.Peer-Reviewed Original ResearchConceptsMutations of Nav1.7Voltage-gated sodium channel Nav1.7Year old patientSodium channel Nav1.7Voltage-clamp studiesErythromelalgia patientsOlder patientsDRG neuronsNav1.7 mutationPainful disordersFunction missense mutationsChannel Nav1.7Neuron firingPatientsRamp stimuliExon 20Channel biophysical propertiesControl allelesNav1.7Missense mutationsBiophysical propertiesMutations
2001
Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)*
Liu C, Dib-Hajj S, Waxman S. Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)*. Journal Of Biological Chemistry 2001, 276: 18925-18933. PMID: 11376006, DOI: 10.1074/jbc.m101606200.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBlotting, WesternCell LineConserved SequenceCytoplasmDNA, ComplementaryDrug ResistanceFibroblast Growth FactorsGene LibraryGlutathione TransferaseGrowth SubstancesHumansMiceModels, BiologicalMolecular Sequence DataNAV1.9 Voltage-Gated Sodium ChannelNeuropeptidesPlasmidsProtein BindingProtein Structure, TertiaryRatsReverse Transcriptase Polymerase Chain ReactionRNASequence Analysis, DNASequence Homology, Amino AcidSodium ChannelsTetrodotoxinTissue DistributionTwo-Hybrid System TechniquesConceptsC-terminusTerminal polypeptideTwo-hybrid screenMammalian cell linesC-terminal regionN-terminal 5Fibroblast growth factor family membersFibroblast growth factor (FGF) familySodium channelsAmino acid residuesFactor family membersGrowth factor family membersCytoplasmic domainFirst growth factorGrowth factor familyFactor familyIntracellular segmentAcid residuesCell membraneFunctional significanceChannel complexDirect interactionCell linesTerminusPolypeptide
2000
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation
Bendahhou S, Cummins T, Hahn A, Langlois S, Waxman S, Ptácek L. A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. Journal Of Clinical Investigation 2000, 106: 431-438. PMID: 10930446, PMCID: PMC314328, DOI: 10.1172/jci9654.Peer-Reviewed Original ResearchConceptsChannel slow inactivationPeriodic paralysisSlow inactivationSodium channel slow inactivationMalignant hyperthermia susceptibilitySkeletal muscle disordersHuman skeletal muscleParalytic attacksMuscle disordersHyperkalemic periodic paralysisSkeletal muscleParalysisDisease-causing mutationsNovel mutationsHyperKPPChannel defectsMolecular determinantsAlpha subunitMutant channelsMutationsDouble mutationInactivationPatientsTransmembrane segments S5Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors
Fjell J, Hjelmström P, Hormuzdiar W, Milenkovic M, Aglieco F, Tyrrell L, Dib-Hajj S, Waxman S, Black J. Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors. Neuroreport 2000, 11: 199-202. PMID: 10683857, DOI: 10.1097/00001756-200001170-00039.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCorneaFemaleGanglia, SpinalImage Processing, Computer-AssistedImmunohistochemistryMolecular Sequence DataMyelin SheathNAV1.9 Voltage-Gated Sodium ChannelNerve FibersNeurons, AfferentNeuropeptidesNociceptorsPresynaptic TerminalsRanvier's NodesRatsRats, Sprague-DawleySciatic NerveSodium ChannelsTetrodotoxinConceptsSciatic nerveSmall diameter primary sensory neuronsSodium currentTetrodotoxin-resistant sodium channelsTetrodotoxin-resistant sodium currentDorsal root ganglion neuronsSodium channelsPrimary sensory neuronsAxonal sodium currentsNodes of RanvierNociceptive transmissionChannel immunoreactivityGanglion neuronsUnmyelinated fibersAxon terminalsSensory neuronsNerveImmunoreactivityAxonsNeuronsSpecific peptidesNociceptorsIB4CorneaAntibodies
1999
Coding Sequence, Genomic Organization, and Conserved Chromosomal Localization of the Mouse Gene Scn11a Encoding the Sodium Channel NaN
Dib-Hajj S, Tyrrell L, Escayg A, Wood P, Meisler M, Waxman S. Coding Sequence, Genomic Organization, and Conserved Chromosomal Localization of the Mouse Gene Scn11a Encoding the Sodium Channel NaN. Genomics 1999, 59: 309-318. PMID: 10444332, DOI: 10.1006/geno.1999.5890.Peer-Reviewed Original ResearchConceptsSodium channel geneChannel genesConserved linkage groupMouse chromosome 9Sodium channel alphaAlternative exon 5Amino acid levelsGenomic organizationChromosomal localizationLinkage groupsHuman genesHuman SCN5ACoding sequenceCommon lineageChannel alphaChromosome 9TTX-R sodium channelsGenesSmall-diameter sensory neuronsTransduction of painDorsal root gangliaHigh-threshold nociceptorsExon 5SCN11A geneSodium channels
1998
Novel splice variants of the voltage-sensitive sodium channel alpha subunit
Oh Y, Waxman S. Novel splice variants of the voltage-sensitive sodium channel alpha subunit. Neuroreport 1998, 9: 1267-1272. PMID: 9631410, DOI: 10.1097/00001756-199805110-00002.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsAnimals, NewbornAstrocytesAstrocytomaBrainBucladesineCalcimycinCells, CulturedGenetic VariationMacromolecular SubstancesModels, MolecularMolecular Sequence DataPolymerase Chain ReactionProtein ConformationRatsRats, Sprague-DawleySodium ChannelsSpinal CordUp-RegulationConceptsChannel alpha subunitNeuroblastoma cellsSpinal cord astrocytesB104 neuroblastoma cellsCultured rat astrocytesChannel mRNA expressionNovel splice variantSplice variantsSodium channel alpha subunitAlpha-subunit mRNASpinal cordCerebral astrocytesUnique regulatory pathwaysAlpha subunitRat astrocytesAstrocytesMRNA expressionSubunit mRNAsMicroM A23187Dibutyryl cAMPPremature truncationCellsExpressionRegulatory pathwaysCord
1995
An orphan nuclear receptor, mROR α, and its spatial expression in adult mouse brain
Matsui T, Sashihara S, Oh Y, Waxman S. An orphan nuclear receptor, mROR α, and its spatial expression in adult mouse brain. Brain Research 1995, 33: 217-226. PMID: 8750880, DOI: 10.1016/0169-328x(95)00126-d.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBinding SitesBlotting, NorthernBrainCell DifferentiationCell LineGene ExpressionHumansIn Situ HybridizationMiceMolecular Sequence DataNeuronsNuclear Receptor Subfamily 1, Group F, Member 1Olfactory BulbOrgan SpecificityReceptors, Cytoplasmic and NuclearReceptors, Retinoic AcidSequence Homology, Amino AcidThalamusTrans-ActivatorsTransfectionTumor Cells, CulturedConceptsResponsive elementActivation of transcriptionThyroid hormone responsive elementRetinoic acid responsive elementNeural cell lineagesAcid-responsive elementLaminin B1 geneOrphan nuclear receptorHormone-responsive elementsRAR beta geneSitu hybridization analysisRetinoic acid receptor-related orphan receptorTranscription factorsAdult mouse brainCotransfection experimentsP19 cellsCell lineagesReceptor-related orphan receptorNorthern hybridizationAcid receptor-related orphan receptorHybridization analysisSpatial expressionOrphan receptorBeta geneNuclear receptors