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ePoster
REGULATION OF K V 4.3 PROTEOSTASIS BY A U-BOX E3 UBIQUITIN LIGASE
Chang Heng Hsiehand 2 co-authors
National Taiwan University
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS05-09AM-435
Presentation
Date TBA
Board: PS05-09AM-435
Event Information
Poster Board
PS05-09AM-435
Poster
View posterAbstract
The voltage-gated potassium channel KV4.3 contributes to transient A-type potassium currents in neurons and is essential for regulating neuronal excitability. Loss-of-function mutations in the human KV4.3 channel have been linked to the neurodegenerative disease spinocerebellar ataxia type 19/22 (SCA19/22). Many SCA19/22-causing human KV4.3 mutant channels are associated with defective KV4.3 proteostasis, including reduced protein stability and impaired membrane trafficking. The molecular mechanisms underlying KV4.3 proteostasis remain incompletely understood. Herein, we identified a U-box E3 ubiquitin ligase as a novel binding partner of the KV4.3 channel in the brain. Co-localization of the E3 ubiquitin ligase with KV4.3 was further demonstrated in the dendrosomatic region of neurons. Overexpression of this U-box E3 ubiquitin ligase markedly decreased KV4.3 protein levels through an ubiquitin-dependent degradation pathway via both the proteasomal and lysosomal pathways. RNAi-based knockdown of the endogenous expression of the E3 ubiquitin ligase significantly upregulated KV4.3 protein level in neurons, as well as notably correcting the defective proteostasis of SCA19/2-associated human KV4.3 mutants. Collectively, these findings are consistent with the notion that this U-box E3 ubiquitin ligase serves as a negative regulator of KV4.3 proteostasis in neurons.
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