2022
LINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasis
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
2015
The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice
Bausch AE, Dieter R, Nann Y, Hausmann M, Meyerdierks N, Kaczmarek LK, Ruth P, Lukowski R. The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice. Learning & Memory 2015, 22: 323-335. PMID: 26077685, PMCID: PMC4478330, DOI: 10.1101/lm.037820.114.Peer-Reviewed Original ResearchConceptsFragile X Mental Retardation ProteinCognitive flexibilityFragile X syndromeNormal working memoryAspects of memoryIntellectual disabilityMental retardation proteinSpatial learning capabilitiesSlack channelsWorking memoryBehavioral tasksReference memorySodium-activated potassium channel SlackHigher brain functionsUnfamiliar situationsBrain functionSevere intellectual disabilityMemoryIntellectual developmentSodium-activated potassium channelsNull mouse modelGeneral locomotor activityX syndromeProper functionLearning capabilities
2004
Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice
von Hehn CA, Bhattacharjee A, Kaczmarek LK. Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice. Journal Of Neuroscience 2004, 24: 1936-1940. PMID: 14985434, PMCID: PMC6730406, DOI: 10.1523/jneurosci.4554-03.2004.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAge FactorsAnimalsAuditory PathwaysBrain StemCerebellumCyclic AMP Response Element-Binding ProteinDisease ProgressionMaleMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBANeuronsNeuropeptidesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedPresbycusisReflex, StartleShaw Potassium ChannelsConceptsCAMP response element-binding proteinResponse element-binding proteinTonotopic axisBL/6 miceElement-binding proteinCochlear hair cell lossPCREB-positive cellsAuditory brainstem neuronsCentral auditory neuronsHair cell lossCBA/JTranscription factor cAMP response element-binding proteinBrainstem neuronsKv3.1 potassium channel geneTrapezoid bodyImpaired miceMedial nucleusAuditory brainstemImmunopositive cellsAuditory neuronsMedial endPotassium channel genesGood hearingCell lossCREB expression
1998
The 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
Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain
Perney T, Marshall J, Martin K, Hockfield S, Kaczmarek L. Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain. Journal Of Neurophysiology 1992, 68: 756-766. PMID: 1432046, DOI: 10.1152/jn.1992.68.3.756.Peer-Reviewed Original ResearchConceptsAdult rat brainRat brainSitu hybridization histochemistryAlpha mRNAThalamic nucleiHigh-frequency firing ratesHybridization histochemistryBeta mRNASubstantia nigra reticulataReticular thalamic nucleusNarrow action potentialsPostnatal day 10Embryonic day 17Alpha mRNA levelsSplice variantsKv3.1 transcriptsProtection assaysHeterogeneous expression patternKv3.1 potassium channel geneOlfactory tubercleVestibular nucleiBrain stemGlobus pallidusSame neuronsInferior colliculus