PUBLICATION

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

Authors
Ogino, K., Low, S.E., Yamada, K., Saint-Amant, L., Zhou, W., Muto, A., Asakawa, K., Nakai, J., Kawakami, K., Kuwada, J.Y., Hirata, H.
ID
ZDB-PUB-150219-4
Date
2015
Source
Proceedings of the National Academy of Sciences of the United States of America   112(9): 2859-64 (Journal)
Registered Authors
Hirata, Hiromi, Kawakami, Koichi, Kuwada, John, Low, Sean, Muto, Akira, Saint-Amant, Louis, Zhou, Weibin
Keywords
escape, touch response, ubiquitin, voltage-gated sodium channel, zebrafish
MeSH Terms
  • Animals
  • Base Sequence
  • Cell Membrane/genetics
  • Cell Membrane/metabolism
  • Molecular Sequence Data
  • Mutation
  • Proteasome Endopeptidase Complex/genetics
  • Proteasome Endopeptidase Complex/metabolism
  • Protein Transport/physiology
  • Proteolysis*
  • RING Finger Domains*
  • Ubiquitin/genetics
  • Ubiquitin/metabolism
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/metabolism*
  • Voltage-Gated Sodium Channels/genetics
  • Voltage-Gated Sodium Channels/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
25691753 Full text @ Proc. Natl. Acad. Sci. USA
Abstract

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.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes