Interruption of post-Golgi STING trafficking activates tonic interferon signaling.

ABSTRACT: Activation of the cGAS-STING pathway is traditionally considered a "trigger-release" mechanism where detection of microbial DNA or cyclic di-nucleotides sets off the type I interferon response. Whether this pathway can be activated without pathogenic ligand exposure is less well understood. Here we show that loss of Golgi-to-lysosome STING cofactors, but not ER-to-Golgi cofactors, selectively activates tonic interferon signalling. Impairment of post-Golgi trafficking extends STING Golgi-dwell time, resulting in elevated immune signalling and protection against infection. Mechanistically, trans-Golgi coiled coil protein GCC2 and several RAB GTPases act as key regulators of STING post-Golgi trafficking. Genomic deletion of these factors potently activates cGAS-STING signalling without instig

SUBMITTER: Tu X 

PROVIDER: S-EPMC9666523 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature