ID | 118576 |
著者 |
Nishino, Kohei
Tokushima University
Yamauchi, Shunya
Tokushima University
|
資料タイプ |
学術雑誌論文
|
抄録 | STING, an endoplasmic reticulum (ER)-resident receptor for cyclic di-nucleotides (CDNs), is essential for innate immune responses. Upon CDN binding, STING moves from the ER to the Golgi, where it activates downstream type-I interferon (IFN) signaling. General cargo proteins exit from the ER via concentration at ER exit sites. However, the mechanism of STING concentration is poorly understood. Here, we visualize the ER exit sites of STING by blocking its transport at low temperature or by live-cell imaging with the cell-permeable ligand bis-pivSATE-2'F-c-di-dAMP, which we have developed. After ligand binding, STING forms punctate foci at non-canonical ER exit sites. Unbiased proteomic screens and super-resolution microscopy show that the Golgi-resident protein ACBD3/GCP60 recognizes and concentrates ligand-bound STING at specialized ER-Golgi contact sites. Depletion of ACBD3 impairs STING ER-to-Golgi trafficking and type-I IFN responses. Our results identify the ACBD3-mediated non-canonical cargo concentration system that drives the ER exit of STING.
|
掲載誌名 |
Cell Reports
|
ISSN | 22111247
|
出版者 | Elsevier
|
巻 | 41
|
号 | 12
|
開始ページ | 111868
|
発行日 | 2022-12-20
|
権利情報 | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
|
著者版フラグ |
出版社版
|
部局 |
先端酵素学研究所
薬学系
|