Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol
Year: 2024
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: Naito Foundation, Uehara Memorial Foundation, Mizutani Foundation for Glycoscience, Japan Agency for Medical Research and Development, Ministry of Education, Culture, Sports, Science and Technology, Daiichi Sankyo Foundation of Life Science, Princess Takamatsu Cancer Research Fund, Research Foundation for Opto-Science and Technology, Japan Society for the Promotion of Science, Core Research for Evolutional Science and Technology, Daiichi Sankyo Europe
Awards: Molecular mechanism underlying STING activation/inactivation with membrane traffic, G1607776443, The molecular mechanism underlying STING signalling, STING小胞クラスターのミクロオートファジー分解機構, Physiological significance of phospholipid asymmetry in Golgi membranes, G2144358466, G2576085165, Microdomain dynamics in the inner leaflet of plasma membranes as revealed by super-resolution microscopy and single-molecule imaging, Unraveling of mechanisms of functional cluster formation of glycolipids and verification of the hierarchical structure by high-resolution single-molecule imaging, G3048749161, G5127227024, G6219943277, 25-ヒドロキシコレステロールによるSTING経路の抑制機構の解明, The molecular mechanism of TBK1 activation in the STING signaling pathway, G6718509927, G6741254851, G7134808224, G7519893723, G7874442324, G7879866177, Optimal signal switching control of traffic signal for road construction work in one-sided alternating traffic sections
OpenAlex ID: W4390741378