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


Journal Article

Following their synthesis in the endoplasmic reticulum (ER), voltage-gated 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.

Full Text

Cited Authors

  • Ogino, K; Low, SE; Yamada, K; Saint-Amant, L; Zhou, W; Muto, A; Asakawa, K; Nakai, J; Kawakami, K; Kuwada, JY; Hirata, H

Published Date

  • March 2015

Published In

Volume / Issue

  • 112 / 9

Start / End Page

  • 2859 - 2864

PubMed ID

  • 25691753

Pubmed Central ID

  • 25691753

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1414002112


  • eng