21QA1405200 (to YHT) the Scientific Research and Innovation Program of Shanghai Education Commission, No. 2019YFA0112000 (to YHT) the National Natural Science Foundation of China, Nos. * Correspondence to: Guo-Yuan Yang, MD, PhD, įunding: This study was supported by the National Key R&D Program of China, No. Thus, ARMH3 bridges STING and PIK4B to generate PI4P for STING transportation andĪctivation, an interaction conserved in all eukaryotes.1Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaĢDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea Armh3 fl/fll Lyz Cre/Cre mice were susceptible to DNA virus challenge in vivo. Consistently,ĭisturbed lipid composition inhibited STING activation, whereas aberrantly elevatedĬellular PI4P led to cGAS-independent STING activation. Through RNAi of other PI4P-binding proteins impaired STING activation.

Disrupting PI4P-dependent lipid transport Upon cGAMP-triggered translocation,ĪRMH3 interacted with STING at the Golgi and recruited phosphatidylinositol 4-kinaseīeta (PI4KB) to synthesize PI4P, which directed STING Golgi-to-endosome trafficking

Protein 3 (ARMH3) as critical for STING activation. We examine the mechanisms underlying STING transport and activation beyond the Golgi.Ī genome-wide CRISPR-Cas9 screen identified Armadillo-like helical domain-containing Reticulum and sulfated glycosaminoglycans-induced polymerization at the Golgi. Is initiated by cyclic-GMP-AMP (cGAMP)-induced translocation from the endoplasmic The cGAS-STING pathway mediates cytoplasmic DNA-triggered innate immunity.

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