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. 2021 Nov 29;9:748485. doi: 10.3389/fcell.2021.748485

FIGURE 1.

FIGURE 1

Crosstalk between cGAS–STING signaling and autophagy in type I IFN production. (1) The cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) pathway of type I interferon (IFN) production. cGAS recognizes cytosolic DNA and catalyzes the formation of cGAMP. cGAMP serves as a second messenger that binds to the CBD domain of STING. Upon binding with cGAMP, the conformation of STING changes, and oligomerized STING then migrates away from the endoplasmic reticulum (ER). The oligomerization of STING activates TBK1 by phosphorylation at serine 365. The activated TBK1 then phosphorylates the CTT pLxIS motif (Ser366) of STING to recruit IRF3. TBK1 in turn phosphorylates IRF3 and induces the IRF3 dimer to enter the nucleus, where it promotes type I IFN production. (2) cGAS–STING triggers autophagy. Once STING is activated by cGAMP, STING migrates from the ER to the Golgi apparatus via the ER–Golgi intermediate compartment (ERGIC). At the ERGIC, STING has been implicated in autophagy induction. STING-containing ERGIC serves as a membrane source of LC3 lipidation and triggers the formation of autophagosomes. Finally, autophagosomes fuse with lysosomes, where their content is degraded.