自然免疫分子STINGの細胞内物質輸送経路による厳密な制御機構（The molecular mechanism that governs the activation and inactivation of the STING signalling pathway)

Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. STING localizes at the endoplasmic reticulum (ER) at the steady state, whereas STING translocates to the Golgi/recycling endosomes/lysosomes upon emergence of cytoplasmic dsDNA. However, the biological significance of the subcellular translocation of STING has not been understood. In the present seminar, we present our recent data including (i) the STING translocation to the Golgi and palmitoylation of STING are essential for TBK1 activation by STING (Nat Commun 2016, PNAS 2018), (ii) STING delivery to lysosomes is essential for termination of the STING immune signalling through microautophagy (Nat Cell Biology in press). We also show how the dysregulation of STING traffic leads to the autoinflammatory disease COPA syndrome (J Exp Med 2020, Nat Commun 2021). The recent clinical application to interfere with the STING signalling pathway will be also discussed.