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ZIRC
ZFIN ID: ZDB-PUB-150219-4
RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels
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.
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
FIGURES
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.

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