STING COPII ER Export Trafficking and Signaling Primed by Phosphorylation Switches.

ABSTRACT: Despite advances in understanding the STING signaling pathway, mechanisms governing cyclic GMP-AMP (cGAMP)-induced STING trafficking out of the endoplasmic reticulum (ER) remain unclear. This study reveals that STING localization is regulated by the balance between coat protein II (COPII)- and coat protein I (COPI)-mediated trafficking, maintaining ER residency in the inactive state or promoting transport to the cis-Golgi via enhanced COPII-mediated export upon activation. Two novel TANK-binding kinase 1 (TBK1)-regulated phosphorylated COPII sorting signals on STING-a conserved pSGME motif and a primate-specific pFS motif-are biochemically and structurally identified. These cGAMP-induced signals drive activated STING toward the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi co

SUBMITTER: Nan Y 

PROVIDER: S-EPMC12463132 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature