Ubiquitin Ligase RNF138 Promotes Episodic Ataxia Type 2-Associated Aberrant Degradation of Human Ca_v2.1 (P/Q-Type) Calcium Channels.

ABSTRACT: Voltage-gated Ca_V2.1 channels comprise a pore-forming α_1A subunit with auxiliary α₂δ and β subunits. Ca_V2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding the Ca_V2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of Ca_V2.1 wild-type (WT) protein expression via aberrant proteasomal degradation. Here, we set out to delineate the protein degradation mechanism of human Ca_V2.1 subunit by identifying RNF138, an E3 ubiquitin ligase, as a novel Ca_V2.1-binding partner. In neurons, RNF138 and Ca_V2.1 coexist in th

SUBMITTER: Fu SJ 

PROVIDER: S-EPMC6596842 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature