Autophagy side of MB21D1/cGAS DNA sensor

The MB21D1/cGAS (Mab-21 domain-containing 1/cyclic GMP-AMP [cGAMP] synthetase), acts as an intracellular pattern recognition receptor (PPR) to sense cytosolic pathogen DNAs and subsequently generates the second messenger cGAMP to initiate the TMEM173/STING pathway for interferon (IFN) production. In...

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Bibliographic Details
Published in:Autophagy 2014-06, Vol.10 (6), p.1146-1147
Main Authors: Liang, Qiming, Seo, Gil Ju, Choi, Youn Jung, Ge, Jianning, Rodgers, Mary A, Shi, Mude, Jung, Jae U
Format: Article
Language:English
Subjects:
Animals
Apoptosis Regulatory Proteins - immunology
Autophagic Punctum
autophagy
Beclin 1
cGAS
DNA - immunology
Herpesvirus 1, Human - immunology
Humans
Immunity, Innate
interferon
Membrane Proteins - immunology
Nucleotidyltransferases - immunology
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Summary:The MB21D1/cGAS (Mab-21 domain-containing 1/cyclic GMP-AMP [cGAMP] synthetase), acts as an intracellular pattern recognition receptor (PPR) to sense cytosolic pathogen DNAs and subsequently generates the second messenger cGAMP to initiate the TMEM173/STING pathway for interferon (IFN) production. Intriguingly, we have recently demonstrated crosstalk between the intracellular DNA sensing pathway and autophagy machinery by demonstrating a direct interaction between the MB21D1 DNA sensor and the BECN1/Beclin 1 autophagy protein. This interaction not only suppresses MB21D1 enzymatic activity to halt cGAMP production, but also enhances the autophagy-mediated degradation of cytosolic microbial DNAs. This demonstrates that MB21D1 is the molecular link between the intracellular DNA sensing pathway and the autophagy pathway, ultimately developing well-balanced immune responses against pathogens.
ISSN:1554-8627
1554-8635
DOI:10.4161/auto.28769