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Autophagy. 2014 Jun;10(6):1146-7. doi: 10.4161/auto.28769.

Autophagy side of MB21D1/cGAS DNA sensor.

Author information

1
Department of Molecular Microbiology and Immunology; Keck School of Medicine; University of Southern California, Los Angeles, CA USA.
2
Department of Molecular Microbiology and Immunology; Keck School of Medicine; University of Southern California, Los Angeles, CA USA; Department of Pharmacology and Pharmaceutical Sciences; School of Pharmacy; University of Southern California; Los Angeles, CA USA.

Abstract

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.

KEYWORDS:

Beclin 1; autophagy; cGAS; interferon

PMID:
24879161
PMCID:
PMC4091176
DOI:
10.4161/auto.28769
[Indexed for MEDLINE]
Free PMC Article
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