2021
Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1
Zhang Y, Varela L, Szigeti-Buck K, Williams A, Stoiljkovic M, Šestan-Peša M, Henao-Mejia J, D’Acunzo P, Levy E, Flavell RA, Horvath TL, Kaczmarek LK. Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1. Nature Communications 2021, 12: 1731. PMID: 33741962, PMCID: PMC7979925, DOI: 10.1038/s41467-021-22003-8.Peer-Reviewed Original ResearchConceptsTank Binding Kinase 1HAX-1Kv3.3 potassium channelMultivesicular bodiesKinase 1TANK-binding kinase 1Activation of caspasesAnti-apoptotic proteinsPotassium channelsMembrane proteinsBiochemical pathwaysCerebellar neuronsChannels bindCell deathTBK1 activityIon channelsMutant channelsCellular constituentsTraffickingKv3.3 channelsProteinNeuronal survivalMutationsChannel inactivationCaspases
2019
Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)
Ali SR, Malone TJ, Zhang Y, Prechova M, Kaczmarek LK. Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1). The FASEB Journal 2019, 34: 1591-1601. PMID: 31914597, PMCID: PMC6956700, DOI: 10.1096/fj.201902366r.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Phosphatase 1Binding of PP1C-terminusCytoplasmic signaling proteinsCytoplasmic C-terminusActin-binding proteinsSlack channelsPKC phosphorylation sitesPhosphoprotein substratesDisease-causing mutationsPhosphorylation sitesSignaling proteinsSlack currentsHuman mutationsSodium-activated potassium channelsPHACTR1Slack genePotassium channelsProteinActinMutationsPatch-clamp recordingsCentral nervous systemMutants
2017
Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance
Kaczmarek LK, Zhang Y. Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance. Physiological Reviews 2017, 97: 1431-1468. PMID: 28904001, PMCID: PMC6151494, DOI: 10.1152/physrev.00002.2017.Peer-Reviewed Original ResearchConceptsKv3 channelsAuditory brain stem neuronsNeurotransmitter releaseBrain stem neuronsOngoing neuronal activityFire action potentialsHigh-frequency firingChannel genesStem neuronsGABAergic interneuronsMultiple protein isoformsCertain neuronsProtein-protein interactionsNeuronal activityNeuronal functionAlzheimer's diseaseNeurological disordersAction potentialsPurkinje cellsUnique expression patternKv3 familyNeuronsAbnormal regulationProtein isoformsProtein kinase
2016
Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex
Fleming MR, Brown MR, Kronengold J, Zhang Y, Jenkins DP, Barcia G, Nabbout R, Bausch AE, Ruth P, Lukowski R, Navaratnam DS, Kaczmarek LK. Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex. Cell Reports 2016, 16: 2281-2288. PMID: 27545877, PMCID: PMC5123741, DOI: 10.1016/j.celrep.2016.07.024.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBiosensing TechniquesBithionolBridged Bicyclo Compounds, HeterocyclicCell MembraneCerebral CortexFragile X Mental Retardation ProteinGene Expression RegulationHEK293 CellsHumansIon TransportMiceMice, KnockoutMicrofilament ProteinsMutationNerve Tissue ProteinsNeuronsPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Sodium-ActivatedPrimary Cell CultureProtein BindingRNA, Small InterferingSignal TransductionThiazolidinesXenopus laevisConceptsProtein phosphatase 1Plasma membraneProtein kinase C.C-terminal residuesPhactr-1Potassium channelsPhosphatase 1Terminal domainSlack channelsHuman mutationsKinase C.Sodium-activated potassium channelsPharmacological activatorsOptical biosensor assayChannel stimulationSlack currentsBiosensor assaysMembraneMutantsPhosphorylationIntellectual disabilityProteinMutationsSevere intellectual disabilityActivatorKv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating
Zhang Y, Zhang XF, Fleming MR, Amiri A, El-Hassar L, Surguchev AA, Hyland C, Jenkins DP, Desai R, Brown MR, Gazula VR, Waters MF, Large CH, Horvath TL, Navaratnam D, Vaccarino FM, Forscher P, Kaczmarek LK. Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating. Cell 2016, 165: 434-448. PMID: 26997484, PMCID: PMC4826296, DOI: 10.1016/j.cell.2016.02.009.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin-Related Protein 2Actin-Related Protein 2-3 ComplexActin-Related Protein 3Adaptor Proteins, Signal TransducingAmino Acid SequenceCell MembraneMolecular Sequence DataMutationNeuronsPluripotent Stem CellsRac GTP-Binding ProteinsShaw Potassium ChannelsSignal TransductionSpinocerebellar AtaxiasConceptsCytoplasmic C-terminusProline-rich domainPlasma membraneHAX-1Actin nucleationC-terminusCortical actin filament networkLocal actin networkStem cell-derived neuronsActin filament networkCell-derived neuronsAnti-apoptotic proteinsActin cytoskeletonKv3.3 potassium channelActin assemblyActin structuresActin networkArp2/3Channel gatingFilament networkGrowth conesCerebellar neurodegenerationKv3.3TerminusPotassium channels
2014
More Than a Pore: Ion Channel Signaling Complexes
Lee A, Fakler B, Kaczmarek LK, Isom LL. More Than a Pore: Ion Channel Signaling Complexes. Journal Of Neuroscience 2014, 34: 15159-15169. PMID: 25392484, PMCID: PMC4228125, DOI: 10.1523/jneurosci.3275-14.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionHumansIon Channel GatingIon ChannelsNeuronsProtein SubunitsProteomicsSignal TransductionConceptsIon channelsHeterologous expression systemIon channel complexSignaling ComplexFunctional dissectionHuman genomeMolecular basisExpression systemSecond messengerHuman diseasesChannel complexCellular excitabilityProteinNew insightsSuch interactionsInteractomeGenomeUnexpected propertiesComplexesMessengerPathwayInteractionDysregulationLocalizationVivoDisrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels
El-Hassar L, Simen AA, Duque A, Patel KD, Kaczmarek LK, Arnsten AF, Yeckel MF. Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels. Biological Psychiatry 2014, 76: 476-485. PMID: 24560582, PMCID: PMC4104266, DOI: 10.1016/j.biopsych.2013.12.019.Peer-Reviewed Original ResearchConceptsCyclic adenosine monophosphateIntracellular Ca2Prefrontal cortical pyramidal neuronsReceptor-mediated intracellular Ca2Regulation of cAMPPrefrontal cortical slicesCortical pyramidal neuronsDISC1 functionMajor depressive disorderPyramidal neuron activityPatch-clamp recordingsTRPC channel activityDISC1 disruptionPrefrontal cortex activityPyramidal neuronsCortical slicesDepressive disorderAdult ratsIntracellular calcium wavesSustained depolarizationViral knockdownNeuron activityBipolar disorderMental disordersCAMP generation
2012
De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy
Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nature Genetics 2012, 44: 1255-1259. PMID: 23086397, PMCID: PMC3687547, DOI: 10.1038/ng.2441.Peer-Reviewed Original Research
2011
Potassium channel modulation and auditory processing
Brown MR, Kaczmarek LK. Potassium channel modulation and auditory processing. Hearing Research 2011, 279: 32-42. PMID: 21414395, PMCID: PMC3137660, DOI: 10.1016/j.heares.2011.03.004.Peer-Reviewed Original ResearchConceptsAuditory brainstem nucleiBrainstem nucleiPotassium channelsPotassium channel modulationSynaptic stimulationFiring patternsOverall sensitivityChannel modulationNeuronsAuditory environmentAuditory processingAuditory systemHigh rateAuditory informationIntrinsic electrical propertiesKey proteinsReview article
2009
Use of optical biosensors to detect modulation of Slack potassium channels by G protein-coupled receptors
Fleming MR, Kaczmarek LK. Use of optical biosensors to detect modulation of Slack potassium channels by G protein-coupled receptors. Journal Of Receptors And Signal Transduction 2009, 29: 173-181. PMID: 19640220, PMCID: PMC3727623, DOI: 10.1080/10799890903056883.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsProtein-coupled receptorsPlasma membraneIon channelsActivation of GPCRsProtein-protein interactionsDistribution of massExcitable cell typesPotassium channelsRefractive indexHeteromeric channel complexesOptical sensorsOptical biosensorSlack potassium channelsSurface of cellsRegulatory proteinsMass distributionGPCR activationSodium-activated potassium channelsLiving cellsCell typesElectrical propertiesChannel complexBiophysical propertiesProtein
2006
Non-conducting functions of voltage-gated ion channels
Kaczmarek LK. Non-conducting functions of voltage-gated ion channels. Nature Reviews Neuroscience 2006, 7: 761-771. PMID: 16988652, DOI: 10.1038/nrn1988.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Adhesion MoleculesCell Physiological PhenomenaCytoskeletonHumansIon ChannelsModels, BiologicalSignal TransductionConceptsMitogen-activated protein kinaseΒ-subunitProtein kinaseIntrinsic protein kinase activityTRP familyΑ-subunitNon-conducting functionCell-cell adhesionTranscription factor activityDependent protein kinase IIProtein kinase activityLarge extracellular domainCell proliferationSynaptic release machineryTranscription factor CREBProtein kinase IIVoltage-gated ion channelsKey PointsIn additionMAPK/ERKIntrinsic enzyme activityNon-selective cation channelsCell adhesion moleculeReductase functionC-terminusKinase activity
2002
Act locally: new ways of regulating voltage-gated ion channels.
McKay SE, Kaczmarek LK. Act locally: new ways of regulating voltage-gated ion channels. Molecular Interventions 2002, 2: 215-8. PMID: 14993392, DOI: 10.1124/mi.2.4.215.Peer-Reviewed Original Research
1998
Direct and indirect regulation of a single ion channel
Magoski N, Kaczmarek L. Direct and indirect regulation of a single ion channel. The Journal Of Physiology 1998, 509: 1-1. PMID: 9547374, PMCID: PMC2230943, DOI: 10.1111/j.1469-7793.1998.001bo.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsThe Expression of Two Splice Variants of the Kv3.1 Potassium Channel Gene Is Regulated by Different Signaling Pathways
Liu S, Kaczmarek L. The Expression of Two Splice Variants of the Kv3.1 Potassium Channel Gene Is Regulated by Different Signaling Pathways. Journal Of Neuroscience 1998, 18: 2881-2890. PMID: 9526005, PMCID: PMC6792597, DOI: 10.1523/jneurosci.18-08-02881.1998.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsCerebellumFibroblast Growth FactorsGene Expression Regulation, DevelopmentalMembrane PotentialsNerve Growth FactorsNeuropeptidesPotassium ChannelsPotassium Channels, Voltage-GatedProtein Kinase CRatsRats, Sprague-DawleyRNA, MessengerSecond Messenger SystemsShaw Potassium ChannelsSignal TransductionTranscription, GeneticConceptsDifferent signaling pathwaysKv3.1 potassium channel genePotassium channel genesBasic fibroblast growth factorChannel genesSignaling pathwaysNuclear protein kinase C activityMRNA levelsDifferent channel proteinsProtein kinase C inhibitorProtein kinase C activityKinase C inhibitorKinase C activityAlternative splicingNuclear RNAChannel proteinsMolecular mechanismsFibroblast growth factorDifferential regulationDevelopmental stagesSplice variantsC inhibitorPKC activityC activityGenes
1992
The role of inositol phosphates in neuronal function.
Perney T, Kaczmarek L. The role of inositol phosphates in neuronal function. 1992, 26: 311-33. PMID: 1419361.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements