STEEP mediates STING ER exit and activation of signaling
Research output: Contribution to journal › Journal article › Research › peer-review
STING ER exit is the rate-limiting step in STING signaling, but the mechanism that drives this process is not understood. Paludan and colleagues identify CxORF56, called STEEP here, as a positive regulator of STING signaling.
STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.
Original language | English |
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Journal | Nature Immunology |
Volume | 21 |
Issue number | 8 |
Pages (from-to) | 868-+ |
Number of pages | 25 |
ISSN | 1529-2908 |
DOIs | |
Publication status | Published - 2020 |
Bibliographical note
Author Correction: STEEP mediates STING ER exit and activation of signaling
DOI: 10.1038/s41590-020-0803-5
- CYCLIC GMP-AMP, INNATE IMMUNITY, DNA VIRUSES, ADAPTER, TRANSLOCATION, PHOSPHORYLATION, 2ND-MESSENGER, AUTOPHAGY, SYNTHASE
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610351/pdf/EMS117976.pdf
Accepted author manuscript
ID: 246784787