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Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity
https://tokushima-u.repo.nii.ac.jp/records/2004705
https://tokushima-u.repo.nii.ac.jp/records/200470520a51764-3e8b-477c-96d7-3319d5a60bcf
| 名前 / ファイル | ライセンス | アクション |
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bbrc_487_4_917.pdf (737 KB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||||||
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| 公開日 | 2018-05-07 | |||||||||||||||||||||||
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| アクセス権 | open access | |||||||||||||||||||||||
| 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 | |||||||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||||||
| 関連識別子 | https://doi.org/10.1016/j.bbrc.2017.05.002 | |||||||||||||||||||||||
| 関連名称 | 10.1016/j.bbrc.2017.05.002 | |||||||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||||||
| 出版タイプ | AM | |||||||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||
| タイトル | Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity | |||||||||||||||||||||||
| 著者 |
ヤマシタ, アリサ
× ヤマシタ, アリサ
× ヒラキ, ユリ
× 山﨑, 哲男
WEKO
403
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| 内容記述 | αB-crystallin (αBC) is a small heat shock protein. Mutations in the αBC gene are linked to α-crystallinopathy, a hereditary myopathy histologically characterized by intracellular accumulation of protein aggregates. The disease-causing R120G αBC mutant, harboring an arginine-to-glycine replacement at position 120, is an aggregate-prone protein. We previously showed that the R120G mutant’s aggregation in HeLa cells was prevented by enforced expression of αBC on the endoplasmic reticulum (ER). To elucidate the molecular nature of the preventive effect on the R120G mutant, we isolated proteins binding to ER-anchored αBC (TMαBC). The ER transmembrane CLN6 protein was identified as a TMαBC's binder. CLN6 knockdown in HeLa cells attenuated TMαBC's anti-aggregate activity against the R120G mutant. Conversely, CLN6 overexpression enhanced the activity, indicating that CLN6 operates as a downstream effector of TMαBC. CLN6 physically interacted with the R120G mutant, and repressed its aggregation in HeLa cells even when TMαBC was not co-expressed. Furthermore, CLN6’s antagonizing effect on the R120G mutant was compromised upon treatment with a lysosomal inhibitor, suggesting CLN6 requires the intact autophagy-lysosome system to prevent the R120G mutant from aggregating. We hence conclude that CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMαBC, but also serves as a potential target of therapeutic interventions. | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | αB-crystallin | |||||||||||||||||||||||
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| 主題 | aggregate | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | CLN6 | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | endoplasmic reticulum | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | neuronal ceroid lipofuscinosis | |||||||||||||||||||||||
| 書誌情報 |
en : Biochemical and Biophysical Research Communications 巻 487, 号 4, p. 917-922, 発行日 2017-05-03 |
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| 収録物ID | ||||||||||||||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||
| 収録物識別子 | 0006291X | |||||||||||||||||||||||
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| 収録物識別子タイプ | NCID | |||||||||||||||||||||||
| 収録物識別子 | AA00564395 | |||||||||||||||||||||||
| 出版者 | ||||||||||||||||||||||||
| 出版者 | Elsevier | |||||||||||||||||||||||
| 権利情報 | ||||||||||||||||||||||||
| 権利情報 | © 2017 Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||||||||||||||||
| EID | ||||||||||||||||||||||||
| 識別子 | 324668 | |||||||||||||||||||||||
| 言語 | ||||||||||||||||||||||||
| 言語 | eng | |||||||||||||||||||||||
