cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette.
Fiche publication
Date publication
janvier 2021
Journal
Faculty reviews
Auteurs
Membres identifiés du Cancéropôle Est :
Pr IMLER Jean-Luc
Tous les auteurs :
Cai H, Imler JL
Lien Pubmed
Résumé
Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway of innate immunity in mammals. It is activated upon binding the cyclic dinucleotide 2'3'-cGAMP, a second messenger produced by the enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), which acts as the receptor for DNA in this pathway, and triggers the expression of interferons and other viral stress-induced genes. The ancient origin of STING in the evolution of animals had been noted, but its primitive function was speculative. We review here recent advances in the remarkable history of cGAS-STING signaling, which establish that cGAS is a member of the family of cGAS/DncV-like nucleotidyltransferases (CD-NTases). In bacteria, CD-NTases synthesize a wide range of cyclic oligonucleotide second messengers in response to bacteriophage infections, which in turn activate a variety of effector proteins to abort phage infection. Among these effectors, some are related to STING, revealing an ancestral function for the cGAS-STING cassette in antiviral host defense. Study of STING signaling in invertebrate animals is consistent with an early acquisition in the history of metazoans of CD-NTase- and STING-encoding genes to counter the universal threat of viruses. In particular, STING-dependent immunity appears to play a previously unsuspected important role in some insects. These discoveries open up interesting perspectives for the use of model organisms to decipher emerging aspects of cGAS-STING biology in mammals, such as the activation of interferon-independent responses or the function and regulation of cGAS in the nucleus.
Mots clés
CBASS, CD-NTase, cGAMP, cGAMP- 2’3’, innate immunity, interferon
Référence
Fac Rev. 2021 ;10:54