| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-07-16 |
| タイトル |
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タイトル |
The Nedd4L ubiquitin ligase is activated by FCHO2-generated membrane curvature |
| 言語 |
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言語 |
eng |
| キーワード |
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主題Scheme |
Other |
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主題 |
Nedd4L |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Endocytosis |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Clathrin |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Endocytosis |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Membrane Curvature |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Sakamoto, Yasuhisa
Uezu, Akiyoshi
Kikuchi, Koji
Kang, Jangmi
Fujii, Eiko
Moroishi, Toshiro
末次, 志郎
Nakanishi, Hiroyuki
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
The C2-WW-HECT domain ubiquitin ligase Nedd4L regulates membrane sorting during endocytosis through the ubiquitination of cargo molecules such as the epithelial sodium channel (ENaC). Nedd4L is catalytically autoinhibited by an intramolecular interaction between its C2 and HECT domains, but the protein’s activation mechanism is poorly understood. Here, we show that Nedd4L activation is linked to membrane shape by FCHO2, a Bin-Amphiphysin-Rsv (BAR) domain protein that regulates endocytosis. FCHO2 was required for the Nedd4L-mediated ubiquitination and endocytosis of ENaC, with Nedd4L co-localizing with FCHO2 at clathrin-coated pits. In cells, Nedd4L was specifically recruited to, and activated by, the FCHO2 BAR domain. Furthermore, we reconstituted FCHO2-induced recruitment and activation of Nedd4L in vitro. Both the recruitment and activation were mediated by membrane curvature rather than protein$2013protein interactions. The Nedd4L C2 domain recognized a specific degree of membrane curvature that was generated by the FCHO2 BAR domain, with this curvature directly activating Nedd4L by relieving its autoinhibition. Thus, we show for the first time a specific function (i.e., recruitment and activation of an enzyme regulating cargo sorting) of membrane curvature by a BAR domain protein. |
| 書誌情報 |
en : The EMBO Journal
巻 43,
号 23,
p. 5883-5909,
ページ数 27,
発行日 2024-12-02
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| 出版者 |
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出版者 |
EMBO Press |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1460-2075 |
| 出版者版DOI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1038/s44318-024-00268-1 |
| 出版者版URI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
URI |
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関連識別子 |
https://www.embopress.org/doi/full/10.1038/s44318-024-00268-1 |
| 権利 |
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|
権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
|
権利情報 |
$00A9 The Author(s). This article is licensed under a Creative Commons Attribution 4.0International License, which permits use, sharing, adaptation, distribution andreproduction in any medium or format, as long as you give appropriate credit tothe original author(s) and the source, provide a link to the Creative Commonslicence, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons licence,unless indicated otherwise in a credit line to the material. If material is notincluded in the article’s Creative Commons licence and your intended use is notpermitted by statutory regulation or exceeds the permitted use, you will need toobtain permission directly from the copyright holder. To view a copy of thislicence, visit http://creativecommons.org/licenses/by/4.0/. Creative Com-mons Public Domain Dedication waiver http://creativecommons.org/public-domain/zero/1.0/ applies to the data associated with this article, unlessotherwise stated in a credit line to the data, but does not extend to the graphicalor creative elements of illustrations, charts, or $FB01gures. This waiver removes legalbarriers to the re-use and mining of research data. According to standardscholarly practice, it is recommended to provide appropriate citation andattribution whenever technically possible. |
| 著者版フラグ |
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出版タイプ |
NA |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
19K06643 |
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研究課題名 |
細胞膜湾曲作用をもつ分子FCHO2によるエンドサイトーシスの制御機構 |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
19K06544 |
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研究課題名 |
ユビキチン化を介したβ1インテグリンの抑制機構とがん悪性化への関与 |
| 助成情報 |
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助成機関名 |
Setsuro Fujii Memorial,The Osaka Foundation forPromotion of Fundamental Medical Research |
| 助成情報 |
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助成機関名 |
Mochida Memorial Foundation |
| 助成情報 |
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助成機関名 |
Takeda Science Foundation |
| 助成情報 |
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助成機関名 |
Uehara Memorial Foundation |
