| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2021-11-25 |
| タイトル |
|
|
タイトル |
Endoplasmic Reticulum Associated Degradation of Spinocerebellar Ataxia-Related CD10 Cysteine Mutant |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
spinocerebellar ataxia |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
CD10 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
disulfide bond |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
endoplasmic reticulum-associated degradation (ERAD) |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
ER quality control |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 作成者 |
Kanuka, Mai
Ouchi, Fuka
Kato, Nagisa
Katsuki, Riko
Ito, Saori
Miura, Kohta
Hikida, Masaki
Tamura, Taku
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Spinocerebellar ataxia (SCA) is one of the most severe neurodegenerative diseases and is often associated with misfolded protein aggregates derived from the genetic mutation of related genes. Recently, mutations in CD10 such as C143Y have been identified as SCA type 43. CD10, also known as neprilysin or neuroendopeptidase, digests functional neuropeptides, such as amyloid beta, in the extracellular region. In this study, we explored the cellular behavior of CD10 C143Y to gain an insight into the functional relationship of the mutation and SCA pathology. We found that wild-type CD10 is expressed on the plasma membrane and exhibits endopeptidase activity in a cultured cell line. CD10 C143Y, however, forms a disulfide bond-mediated oligomer that does not appear by the wild-type CD10. Furthermore, the CD10 C143Y mutant was retained in the endoplasmic reticulum (ER) by the molecular chaperone BiP and was degraded through the ER-associated degradation (ERAD) process, in which representative ERAD factors including EDEM1, SEL1L, and Hrd1 participate in the degradation. Suppression of CD10 C143Y ERAD recovers intracellular transport but not enzymatic activity. Our results indicate that the C143Y mutation in CD10 negatively a ects protein maturation and results in ER retention and following ERAD. These findings provide beneficial insight into SCA type 43 pathology. |
|
言語 |
en |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 書誌情報 |
International Journal of Molecular Sciences
巻 21,
号 12,
p. 4237,
発行日 2020
|
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1422-0067 |
| 出版者 |
|
|
出版者 |
MDPI |
| 関連情報 |
|
|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.3390/ijms21124237 |
| 権利情報 |
|
|
権利情報 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
riA_2021_9 (3.3 MB)
