RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels
| Autor: | Sean E. Low, Kazutoyo Ogino, John Y. Kuwada, Weibin Zhou, Kazuhide Asakawa, Junichi Nakai, Hiromi Hirata, Louis Saint-Amant, Kenta Yamada, Akira Muto, Koichi Kawakami |
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| Rok vydání: | 2015 |
| Předmět: |
Proteasome Endopeptidase Complex
Ubiquitin-Protein Ligases Mutant Molecular Sequence Data Voltage-Gated Sodium Channels Biology Cell membrane Ubiquitin medicine Animals Zebrafish chemistry.chemical_classification DNA ligase Multidisciplinary Base Sequence Sodium channel Endoplasmic reticulum Cell Membrane Zebrafish Proteins Biological Sciences Axon initial segment Transport protein Cell biology Protein Transport medicine.anatomical_structure chemistry Biochemistry Mutation Proteolysis biology.protein RING Finger Domains |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 112(9) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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