Activation of STING requires palmitoylation at the Golgi

By Kojiro Mukai, Hiroyasu Konno, Tatsuya Akiba, Takefumi Uemura, S. Waguri, Toshihide Kobayashi, G. Barber, H. Arai, T. Taguchi. Nature Communications, 2016

635 citations recorded by the source corpus.

Stimulator of interferon genes (STING) is essential for the type I interferon response against DNA pathogens. In response to the presence of DNA and/or cyclic dinucleotides, STING translocates from the endoplasmic reticulum to perinuclear compartments. However, the role of this subcellular translocation remains poorly defined. Here we show that palmitoylation of STING at the Golgi is essential for activation of STING. Treatment with palmitoylation inhibitor 2-bromopalmitate (2-BP) suppresses palmitoylation of STING and abolishes the type I interferon response. Mutation of two membrane-proximal Cys residues (Cys88/91) suppresses palmitoylation, and this STING mutant cannot induce STING-dependent host defense genes. STING variants that constitutively induce the type I interferon response were found in patients with autoimmune diseases. The response elicited by these STING variants is effectively inhibited by 2-BP or an introduction of Cys88/91Ser mutation. Our results may lead to new treatments for cytosolic DNA-triggered autoinflammatory diseases. STING is essential for the type I interferon immune response to foreign DNA. Here, the authors show that palmitoylation of STING at the Golgi is required for activating downstream signalling, and increased Golgi localization of certain STING variants may cause autoimmune disease in some cases.

Subfields: Immunology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6ea8e4d68360bc6982a85f6305196a58fd35f400

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Ablasser
2. Zhijian J. Chen
3. Shizuo Akira
4. N. Perkins
5. Tuo Li
6. G. Barber
7. Ivan Dikic
8. Taro Kawai

In Infectious Diseases

1. A. Ablasser
2. Zhijian J. Chen

In Molecular Biology

1. A. Ablasser
2. Zhijian J. Chen

Citations in the corpus

• cGAS in action: Expanding roles in immunity and inflammation (2019, background): “This process occurs at the Golgi and may explain the requirement to traffic to this specific organelle (23).”
• Role of neuroinflammation in neurodegeneration development (2023, background): “cGAMP produced by cGAS activation binds to STING which is located on the membrane of endoplasmic reticulum (ER)(391) and leads to the translocation of STING from ER to the Golgi where it is further modified.(392) On reaching the Golgi compartment, STING then recruits TBK1, which then activates IRF3 ”