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