Identification of MKRN1 as a second E3 ligase for Eag1 potassium channels reveals regulation via differential degradation.

ABSTRACT: Mutations in the human gene encoding the neuron-specific Eag1 voltage-gated K⁺ channel are associated with neurodevelopmental diseases, indicating an important role of Eag1 during brain development. A disease-causing Eag1 mutation is linked to decreased protein stability that involves enhanced protein degradation by the E3 ubiquitin ligase cullin 7 (CUL7). The general mechanisms governing protein homeostasis of plasma membrane- and endoplasmic reticulum (ER)-localized Eag1 K⁺ channels, however, remain unclear. By using yeast two-hybrid screening, we identified another E3 ubiquitin ligase, makorin ring finger protein 1 (MKRN1), as a novel binding partner primarily interacting with the carboxyl-terminal region of Eag1. MKRN1 mainly interacts with ER-localized immature c

SUBMITTER: Fang YC 

PROVIDER: S-EPMC8039722 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature