RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

Kazutoyo Ogino, Sean E. Low, Kenta Yamada, Louis Saint-Amant, Weibin Zhou, Akira Muto, Kazuhide Asakawa, Junichi Nakai, Koichi Kawakami, John Y. Kuwada, Hiromi Hirata

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Following their synthesis in the endoplasmic reticulum (ER), voltagegated sodium channels (NaV) are transported to the membranes of excitable cells, where they often cluster, such as at the axon initial segment of neurons. Although the mechanisms by which NaV channels form and maintain clusters have been extensively examined, the processes that govern their transport and degradation have received less attention. Our entry into the study of these processes began with the isolation of a new allele of the zebrafish mutant alligator, which we found to be caused by mutations in the gene encoding really interesting new gene (RING) finger protein 121 (RNF121), an E3-ubiquitin ligase present in the ER and cis-Golgi compartments. Here we demonstrate that RNF121 facilitates two opposing fates of NaV channels: (i) ubiquitin-mediated proteasome degradation and (ii) membrane localization when coexpressed with auxiliary NaVβ subunits. Collectively, these results indicate that RNF121 participates in the quality control of NaV channels during their synthesis and subsequent transport to the membrane.

Original languageEnglish
Pages (from-to)2859-2864
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number9
DOIs
Publication statusPublished - 2015 Mar 3
Externally publishedYes

Keywords

  • Escape
  • Touch response
  • Ubiquitin
  • Voltage-gated sodium channel
  • Zebrafish

ASJC Scopus subject areas

  • General

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