Journal
ISCIENCE
Volume 24, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.103473
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [19H03365, 16H05084, 24390014, 21117005, 21117001, 14657577]
- Japan Society for the Promotion of Science (JSPS)
- Japan Science and Technology Agency (JST)
- Program for the Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN)
- Japan Science and Technology Agency
- National Institutes of Health [AI07495]
- Takeda Science Foundation
- Mitsubishi Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Uehara Memorial Foundation
- Naito Foundation
- Global COE Research Grant (Tohoku University EcosystemAdaptability)
- Biotechnological and Biological Research Sciences Council (UK) [BB/E011438/1]
- BBSRC [BB/E011438/1] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [14657577, 21117001, 16H05084, 19H03365, 21117005] Funding Source: KAKEN
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The study demonstrates that the NF-kappa B signaling pathway in Drosophila is activated through a pathway parallel to the Toll receptor, involving the receptor-type guanylate cyclase Gyc76C. This pathway produces cGMP and modulates NF-kappa B signaling to combat bacterial infections. Furthermore, the modulation of NF-kappa B activation by the cGMP signaling pathway is evolutionarily conserved in both fruit flies and human cells.
The nuclear factor-kappa B (NF-kappa B) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation.Here, we show that Drosophila NF-kappa B signaling is activated via a pathway in parallel with the Toll receptor by receptor-type guanylate cyclase, Gyc76C.Gyc76C produces cyclic guanosine monophosphate (cGMP) and modulates NF-kappa B signaling through the downstream Tollreceptor components dMyd88,Pelle, Tube, and Dif/Dorsal (NF-kappa B). The cGMP signaling pathway comprises a membrane-localized cGMP-dependent protein kinase (cGK) called DG2 and protein phosphatase 2A (PP2A) and is crucial for host survival against Gram-positive bacterial infections in Drosophila. A membrane-bound cGK, PRKG2, also modulates NF-kappa B activation via PP2A in human cells, indicating that modulation of NF-kappa B activation in innate immunity by the cGMP signaling pathway is evolutionarily conserved.
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