| アイテムタイプ |
itemtype_ver1(1) |
| 公開日 |
2025-12-02 |
| タイトル |
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タイトル |
Retention of DLK1 in the endoplasmic reticulum identifies roles for EGF-like-domain-specific O-glycans in the secretory pathway |
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言語 |
en |
| 著者 |
Tashima, Yuko
Tsukamoto, Yohei
Tsukamoto, Natsumi
Kondo, Yuji
Uddin, Ehsan
Furukawa, Wakako
Go, Shiori
Arakawa, Hiromu
Kaji, Hiroyuki
Takeuchi, Hideyuki
Okajima, Tetsuya
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| アクセス権 |
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アクセス権 |
embargoed access |
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アクセス権URI |
http://purl.org/coar/access_right/c_f1cf |
| 権利 |
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権利情報 |
"This is the peer reviewed version of the following article: [Tashima, Y., Tsukamoto, Y., Tsukamoto, N., Kondo, Y., Uddin, E., Furukawa, W., Go, S., Arakawa, H., Kaji, H., Takeuchi, H. and Okajima, T. (2025), Retention of DLK1 in the endoplasmic reticulum identifies roles for EGF-like-domain-specific O-glycans in the secretory pathway. FEBS J, 292: 5355-5381. https://doi.org/10.1111/febs.70168], which has been published in final form at [https://doi.org/10.1111/febs.70168]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited." |
|
言語 |
en |
| 内容記述 |
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内容記述タイプ |
Abstract |
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内容記述 |
In the endoplasmic reticulum (ER), O-glycosylation by O-fucose, O-glucose, and O-N-acetylglucosamine (O-GlcNAc) occur in the epidermal growth factor-like (EGF) domains of secreted or transmembrane glycoproteins. Previous studies on Notch receptors have revealed the pivotal role of these O-glycans in the cell surface expression of Notch and secretion of truncated Notch fragments. Although it has been demonstrated that O-fucose, O-glucose and O-GlcNAc stabilize individual EGF domains, their role in the secretory pathway following the completion of the folding process remains unexplored. In this study, we used delta-like homolog 1 (DLK1) containing six consecutive EGF domains as a model glycoprotein to investigate the role of EGF-domain-specific O-glycans in the secretory pathway. Semi-quantitative site-specific glycoproteomics of recombinantly expressed DLK1 revealed multiple O-fucose and O-glucose modifications, along with an unusual EGF-domain-specific O-linked N-acetylglucosamine transferase (EOGT)-dependent O-hexose modification. Consistent with the results of the secretion assay, inactivation of the glycosyltransferases modifying O-fucose and O-glucose, but not the newly identified O-hexose, perturbed the transport of DLK1 from the ER during retention, as assessed using the selective hooks (RUSH) system. Importantly, the absence of O-fucose did not affect O-glucose modification within the same EGF domain, and vice versa. Since protein O-fucosyltransferase 1 and protein O-glucosyltransferase 1 activities depend on the folded state of the EGF domains, O-glycans affected DLK1 transport independently of the folding process required for O-glycosylation in the ER. These findings highlight the distinct roles of O-glycans in facilitating the transport of DLK1 from the ER to the cell surface. |
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言語 |
en |
| 出版者 |
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出版者 |
Wiley |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプresource |
http://purl.org/coar/resource_type/c_6501 |
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タイプ |
journal article |
| 出版タイプ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連情報 |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1111/febs.70168 |
| 収録物識別子 |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
1742-464X |
| 書誌情報 |
en : FEBS JOURNAL
巻 292,
号 20,
p. 5355-5381,
発行日 2025-10
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| ファイル公開日 |
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日付 |
2026-10-01 |
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日付タイプ |
Available |
DLK1-Manuscript.pdf (3.3 MB)
