AsianScientist (Jul. 6, 2016) – Researchers at the University of Tokyo have revealed the mechanism underlying the activation of STING, an innate immune sensor that triggers inflammation to remove foreign pathogens.
This discovery, published in Nature Communications, provides therapeutic targets for treating infections and inflammatory diseases.
When cells are infected with foreign matter such as DNA viruses or bacteria, the foreign DNA is sensed by STING, which is embedded in the membrane of the endoplasmic reticulum (ER), an important site of protein production in a cell. STING then triggers the release of type I interferon and other inflammatory responses to eliminate the foreign substance. This essential basic cellular response is part of the innate immune system that recognizes and eliminates pathogens from our bodies.
However, it was unclear why STING responded to foreign DNA. Additionally, although it is known that STING translocates from the ER to a location close to the nucleus when it detects foreign DNA, the role of this translocation remained unknown.
In the present study, the research group of Assistant Professor Kojiro Mukai, Associate Professor Tomohiko Taguchi and Professor Hiroyuki Arai at the University of Tokyo Graduate School of Pharmaceutical Sciences found that STING is activated at the Golgi, a part of the cell that is involved in protein transport, as opposed to the ER.
Furthermore, the activation of STING requires palmitoylation, a type of protein modification, at the Golgi. The unique lipid environment of the Golgi is also essential for the activation of STING.
In various inflammatory diseases such as autoimmune disease and cancer, STING is often activated, causing an abnormal inflammatory response. Thus, the findings offer new opportunities to treat such diseases by suppressing the palmitoylation of STING or the manipulation of the Golgi lipid composition.
The article can be found at: Mukai et al. (2016) Activation of STING Requires Palmitoylation at the Golgi.
Source: University of Tokyo; Photo: Shutterstock.
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