2021
Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice
Zhang Y, Quraishi IH, McClure H, Williams LA, Cheng Y, Kale S, Dempsey GT, Agrawal S, Gerber DJ, McManus OB, Kaczmarek LK. Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice. The FASEB Journal 2021, 35: e22053. PMID: 34820911, PMCID: PMC8630780, DOI: 10.1096/fj.202101356r.Peer-Reviewed Original ResearchConceptsHAX-1Wild-type animalsMultivesicular bodiesKv3.3 channelsLate endosomes/multivesicular bodiesTank Binding Kinase 1Type animalsCell survival proteinsDisease-causing mutationsVoltage-dependent potassium channelsSpinocerebellar ataxia type 13Survival proteinsKinase 1Mature intact animalsTBK1 activationAge-matched wild-type animalsLevels of CD63Progressive cerebellar degenerationWild-type miceMutationsProtein levelsMutant micePotassium channelsDependent potassium channelsType miceCerebellar 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
2016
Kv3.3 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