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Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics.
http://hdl.handle.net/10422/00013199
http://hdl.handle.net/10422/00013199cc94af9d-d647-4391-9854-3974845d5ee7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-02-01 | |||||
| タイトル | ||||||
| タイトル | Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics. | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Brugada syndrome | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | heat shock protein | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | protein interaction | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | sodium channel | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | ubiquitination | |||||
| 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 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
NGUYEN, Le Kim Chi
× NGUYEN, Le Kim Chi× SHIMIZU, Akio× SOH, Joanne Ern Chi× KOMENO, Masahiro× SATO, Akira× OGITA, Hisakazu |
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| 著者別名 |
清水, 昭男
× 清水, 昭男× 米野, 雅大× 佐藤, 朗× 扇田, 久和 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Transmembrane protein 168 (TMEM168) was found to be localized on the nuclear membrane. A heterozygous mutation (c.1616G>A, p. R539Q) in TMEM168 was identified in patients with Brugada syndrome. This mutation reduced expression of cardiomyocyte sodium channel Nav1.5 via Nedd4-2 E3 ubiquitin ligase-induced ubiquitination and degradation. However, the detailed molecular mechanism provoked by the TMEM168 mutant remains unclear. Here, we demonstrated that small heat shock protein αB-crystallin, which can bind to Nav1.5 and Nedd4-2 and interfere with the association of both proteins, was strongly recruited from the cell surface to the perinuclear region because of the much higher affinity of αB-crystallin with the TMEM168 mutant than with wild-type TMEM168. Following knockdown of αB-crystallin in HL-1 cardiomyocytes, the interaction of Nav1.5 with Nedd4-2 was increased, despite the reduced expression of Nav1.5. Moreover, reduction of Nav1.5 expression by αB-crystallin knockdown was rescued in the presence of a proteasome inhibitor MG-132, suggesting the importance of the αB-crystallin-modulated ubiquitin-proteasome system for the stability of Nav1.5 expression. Collectively, the balance of molecular interactions among Nav1.5, Nedd4-2 and αB-crystallin plays a role in the regulation of cardiomyocyte cell surface expression of Nav1.5, and the TMEM168 mutant disturbs this balance, resulting in a decrease in Nav1.5 expression. | |||||
| 言語 | en | |||||
| 書誌情報 |
en : Journal of biochemistry 巻 170, 号 5, p. 577-585, 発行日 2021-12-28 |
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| 出版者 | ||||||
| 出版者 | Oxford University Press | |||||
| 言語 | en | |||||
| ISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 1756-2651 | |||||
| PMID | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 34086898 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1093/jb/mvab066 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | ©The Author(s) 2021. | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved | |||||
| 著者版フラグ | ||||||
| 出版タイプ | NA | |||||
| 出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
