ALG2 regulates type I interferon responses by inhibiting STING trafficking
| Autor: | Xiaoyu Xu, Xinqi Liu, Lianfei Zhang, Wangsheng Ji |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Innate immune system
Endoplasmic reticulum Calcium-Binding Proteins Membrane Proteins chemistry.chemical_element Herpes Simplex Chromosomal translocation Herpesvirus 1 Human Cell Biology Biology Calcium Immunity Innate eye diseases Cell biology Sting Cytosol chemistry Interferon Interferon Type I medicine Humans Apoptosis Regulatory Proteins Gene medicine.drug |
| Zdroj: | Journal of Cell Science. 134 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.259060 |
| Popis: | Stimulator of IFN genes (STING), an endoplasmic reticulum (ER) signaling adaptor, is essential for the type I interferon response to cytosolic double-stranded DNA. Translocation from the ER to perinuclear vesicles following cyclic GMP–AMP (cGAMP) binding is a critical step for STING to activate downstream signaling molecules, which leads to the production of interferon and pro-inflammatory cytokines. Here, we found that apoptosis-linked gene 2 (ALG2, also known as PDCD6) suppressed STING signaling induced by herpes simplex virus-1 (HSV-1) infection or cGAMP presence. Knockout of ALG2 markedly increased the expression of type I interferons upon cGAMP treatment or HSV-1 infection in THP-1 monocytes. Mechanistically, ALG2 associated with the C-terminal tail of STING and inhibited its trafficking from the ER to the perinuclear region. Furthermore, the ability of ALG2 to coordinate Ca2+ was crucial for its regulation of STING trafficking and DNA-induced innate immune responses. This work suggests that ALG2 is involved in DNA-induced innate immune responses by regulating STING trafficking. |
| Databáze: | OpenAIRE |
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