Description
Cyclic GMP-AMP (cGAMP) synthase (cGAS) (161-522) is a truncated form of cGAS that contains the nucleotidyltransferase and Mab21 domains. cGAS is a nucleotidyltransferase located in the cytosol that acts as a cytosolic DNA sensor to detect foreign DNA from microbial pathogens as part of the innate immune response. Upon binding to cytosolic DNA, cGAS produces the cyclic dinucleotide second messenger cGAMP, which activates stimulator of interferon genes (STING), leading to activation of the type I interferon (IFN) pathway.
In vitro, fibroblasts, macrophages, and dendritic cells isolated from cGAS knockout (cGAS
-/-) mice do not produce type I IFNs following DNA transfection or DNA virus infection. Similarly, cells containing a frame-shift mutation in the cGAS locus fail to mount an immune response to HIV and other retroviruses.
In vivo, cGAS
-/- mice infected with herpes simplex virus 1 (HSV-1) have lower levels of IFN-α and IFN-β, shorter survival times, and higher post-mortem levels of HSV-1 in the brain.
References
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10.4049/jimmunol.1601909[2] LIJUN SUN. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway[J]. Science, 2012, 339 6121.
[3] JIAXI WU. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.[J]. Science, 2013, 339 6121: 826-830. DOI:
10.1126/science.1229963[4] ANDREA ABLASSER. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING[J]. Nature, 2013, 498 7454: 380-384. DOI:
10.1038/nature12306[5] XIAO-DONG LI. Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects[J]. Science, 2013, 341 6152. DOI:
10.1126/science.1244040[6] DAXING GAO. Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses[J]. Science, 2013, 341 6148. DOI:
10.1126/science.1240933
