Evolutionary Origins of cGAS-STING Signaling

Publication date: Available online 14 April 2017
Source:Trends in Immunology
Author(s): Shally R. Margolis, Stephen C. Wilson, Russell E. Vance
Detection of foreign nucleic acids is an important strategy for innate immune recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger cGAMP to activate the signaling adaptor STING. While induction of antiviral type I interferons (IFNs) is the major outcome of STING activation in vertebrates, it has recently become clear that core components of the cGAS-STING pathway evolved more than 600 million years ago, predating the evolution of type I IFNs. Here we discuss the evolutionary origins of the cGAS-STING pathway, and consider the possibility that the ancestral functions of STING may have included activation of antibacterial immunity.



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