RRC ID 33611
著者 Ogino K, Low SE, Yamada K, Saint-Amant L, Zhou W, Muto A, Asakawa K, Nakai J, Kawakami K, Kuwada JY, Hirata H.
タイトル RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 112(9)
ページ 2859-64
公開日 2015-3-3
DOI 10.1073/pnas.1414002112
PII 1414002112
PMID 25691753
PMC PMC4352840
MeSH 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*
IF 9.412
引用数 10
WOS 分野 NEUROSCIENCES
リソース情報
ゼブラフィッシュ SAIGFF213A UASGCaMP7a32A? UASRFP1A ?