Pin1 promotes human Ca_V2.1 channel polyubiquitination by RNF138: pathophysiological implication for episodic ataxia type 2.

ABSTRACT: Loss-of-function mutations in the human gene encoding the neuron-specific Ca²⁺ channel Ca_V2.1 are linked to the neurological disease episodic ataxia type 2 (EA2), as well as neurodevelopmental disorders such as developmental delay and developmental epileptic encephalopathy. Disease-associated Ca_V2.1 mutants may exhibit defective proteostasis and promote endoplasmic reticulum (ER)-associated degradation of their wild-type (WT) counterpart in a dominant-negative manner. The E3 ubiquitin ligase RNF138 was previously shown to mediate EA2-related aberrant degradation of Ca_V2.1 at the ER. Herein we aimed to elucidate the ER proteostasis mechanism of Ca_V2.1. The peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) was identified as

SUBMITTER: Fu SJ 

PROVIDER: S-EPMC11603662 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature