ダウンロード数: 146

このアイテムのファイル:
ファイル 記述 サイズフォーマット 
s41556-023-01098-9.pdf23.95 MBAdobe PDF見る/開く
タイトル: STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes
著者: Kuchitsu, Yoshihiko
Mukai, Kojiro
Uematsu, Rei
Takaada, Yuki
Shinojima, Ayumi
Shindo, Ruri
Shoji, Tsumugi
Hamano, Shiori
Ogawa, Emari
Sato, Ryota
Miyake, Kensuke
Kato, Akihisa
Kawaguchi, Yasushi
Nishitani-Isa, Masahiko
Izawa, Kazushi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-1080-0936 (unconfirmed)
Nishikomori, Ryuta
Yasumi, Takahiro
Suzuki, Takehiro
Dohmae, Naoshi
Uemura, Takefumi
Barber, Glen N.
Arai, Hiroyuki
Waguri, Satoshi
Taguchi, Tomohiko
著者名の別形: 朽津, 芳彦
向井, 康治朗
植松, 黎
高阿田, 有希
篠島, あゆみ
進藤‌, 瑠璃
東海林, 紬
濱野, 栞里
小川, 笑満里
佐藤, 亮太
三宅, 健介
加藤, 哲久
川口, 寧
伊佐, 真彦
井澤, 和司
西小森, 隆太
八角, 高裕
鈴木, 健裕
堂前, 直
植村, 武文
新井, 博之
和栗, 聡
田口, 友彦
キーワード: Autophagy
ESCRT
Innate immunity
Lysosomes
発行日: Mar-2023
出版者: Springer Nature
誌名: Nature Cell Biology
巻: 25
号: 3
開始ページ: 453
終了ページ: 466
抄録: Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs.
記述: STING炎症シグナルの終結分子機構 --新規細胞内分解システムの発見--. 京都大学プレスリリース. 2023-03-14.
著作権等: © The Author(s) 2023
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
URI: http://hdl.handle.net/2433/279876
DOI(出版社版): 10.1038/s41556-023-01098-9
PubMed ID: 36918692
関連リンク: https://www.kyoto-u.ac.jp/ja/research-news/2023-03-14-1
出現コレクション:学術雑誌掲載論文等

アイテムの詳細レコードを表示する

Export to RefWorks


出力フォーマット 


このアイテムは次のライセンスが設定されています: クリエイティブ・コモンズ・ライセンス Creative Commons