Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol
Abstract Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol. STING may function as a scaffold to activate TANK-binding kinase 1 (TBK1), but direct cellular evidence remains lacking. Here we show, using single-molecule...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44317-5 |
| _version_ | 1827382143028822016 |
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| author | Haruka Kemmoku Kanoko Takahashi Kojiro Mukai Toshiki Mori Koichiro M. Hirosawa Fumika Kiku Yasunori Uchida Yoshihiko Kuchitsu Yu Nishioka Masaaki Sawa Takuma Kishimoto Kazuma Tanaka Yasunari Yokota Hiroyuki Arai Kenichi G. N. Suzuki Tomohiko Taguchi |
| author_facet | Haruka Kemmoku Kanoko Takahashi Kojiro Mukai Toshiki Mori Koichiro M. Hirosawa Fumika Kiku Yasunori Uchida Yoshihiko Kuchitsu Yu Nishioka Masaaki Sawa Takuma Kishimoto Kazuma Tanaka Yasunari Yokota Hiroyuki Arai Kenichi G. N. Suzuki Tomohiko Taguchi |
| author_sort | Haruka Kemmoku |
| collection | DOAJ |
| description | Abstract Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol. STING may function as a scaffold to activate TANK-binding kinase 1 (TBK1), but direct cellular evidence remains lacking. Here we show, using single-molecule imaging of STING with enhanced time resolutions down to 5 ms, that STING becomes clustered at the trans-Golgi network (about 20 STING molecules per cluster). The clustering requires STING palmitoylation and the Golgi lipid order defined by cholesterol. Single-molecule imaging of TBK1 reveals that STING clustering enhances the association with TBK1. We thus provide quantitative proof-of-principle for the signaling STING scaffold, reveal the mechanistic role of STING palmitoylation in the STING activation, and resolve the long-standing question of the requirement of STING translocation for triggering the innate immune signaling. |
| first_indexed | 2024-03-08T14:15:17Z |
| format | Article |
| id | doaj.art-849720d0fa4c450ab8549105c9a57319 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T14:15:17Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-849720d0fa4c450ab8549105c9a573192024-01-14T12:28:21ZengNature PortfolioNature Communications2041-17232024-01-0115111710.1038/s41467-023-44317-5Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterolHaruka Kemmoku0Kanoko Takahashi1Kojiro Mukai2Toshiki Mori3Koichiro M. Hirosawa4Fumika Kiku5Yasunori Uchida6Yoshihiko Kuchitsu7Yu Nishioka8Masaaki Sawa9Takuma Kishimoto10Kazuma Tanaka11Yasunari Yokota12Hiroyuki Arai13Kenichi G. N. Suzuki14Tomohiko Taguchi15Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityUnited Graduate School of Agricultural Science, Gifu UniversityInstitute for Glyco-core Research (iGCORE), Gifu UniversityDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of TokyoLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityResearch and Development, Carna Biosciences, Inc.Research and Development, Carna Biosciences, Inc.Division of Molecular Interaction, Institute for Genetic Medicine, Hokkaido University Graduate School of Life ScienceDivision of Molecular Interaction, Institute for Genetic Medicine, Hokkaido University Graduate School of Life ScienceDepartment of EECE, Faculty of Engineering, Gifu UniversityDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of TokyoInstitute for Glyco-core Research (iGCORE), Gifu UniversityLaboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityAbstract Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol. STING may function as a scaffold to activate TANK-binding kinase 1 (TBK1), but direct cellular evidence remains lacking. Here we show, using single-molecule imaging of STING with enhanced time resolutions down to 5 ms, that STING becomes clustered at the trans-Golgi network (about 20 STING molecules per cluster). The clustering requires STING palmitoylation and the Golgi lipid order defined by cholesterol. Single-molecule imaging of TBK1 reveals that STING clustering enhances the association with TBK1. We thus provide quantitative proof-of-principle for the signaling STING scaffold, reveal the mechanistic role of STING palmitoylation in the STING activation, and resolve the long-standing question of the requirement of STING translocation for triggering the innate immune signaling.https://doi.org/10.1038/s41467-023-44317-5 |
| spellingShingle | Haruka Kemmoku Kanoko Takahashi Kojiro Mukai Toshiki Mori Koichiro M. Hirosawa Fumika Kiku Yasunori Uchida Yoshihiko Kuchitsu Yu Nishioka Masaaki Sawa Takuma Kishimoto Kazuma Tanaka Yasunari Yokota Hiroyuki Arai Kenichi G. N. Suzuki Tomohiko Taguchi Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol Nature Communications |
| title | Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol |
| title_full | Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol |
| title_fullStr | Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol |
| title_full_unstemmed | Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol |
| title_short | Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol |
| title_sort | single molecule localization microscopy reveals sting clustering at the trans golgi network through palmitoylation dependent accumulation of cholesterol |
| url | https://doi.org/10.1038/s41467-023-44317-5 |
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