scholarly journals ABCC1/MRP1 exports cGAMP and modulates cGAS-dependent immunity

2021 ◽  
Author(s):  
Joanna H. Maltbaek ◽  
Jessica M. Snyder ◽  
Daniel B. Stetson
Keyword(s):  
Mouse Model ◽  
Cyclic Gmp ◽  
Regulatory Mechanism ◽  
Type I Interferon ◽  
Type I ◽  
Adapter Protein ◽  
Dna Sensor ◽  
Interferon Production ◽  
Sting Pathway ◽  
Cyclic Dinucleotide

AbstractThe DNA sensor cyclic GMP-AMP synthase (cGAS) is important for antiviral and anti-tumor immunity. cGAS generates cyclic GMP-AMP (cGAMP), a diffusible cyclic dinucleotide that activates the antiviral response through the adapter protein Stimulator of Interferon Genes (STING). cGAMP is negatively charged and cannot passively cross cell membranes, but recent advances have established a role for extracellular cGAMP as an “immunotransmitter” that can be imported into cells. However, the mechanism by which cGAMP exits cells remains unknown. Here, we identify ABCC1/MRP1 as an ATP-dependent cGAMP exporter that influences STING signaling and type I interferon production. We demonstrate that ABCC1 deficiency exacerbates cGAS-dependent autoimmunity in the Trex1-/- mouse model of Aicardi-Goutières syndrome. These studies identify ABCC1-mediated cGAMP export as a key regulatory mechanism of the cGAS-STING pathway.

scholarly journals The Innate Immune cGAS-STING-Pathway in Cardiovascular Diseases – A Mini Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Lavinia Rech ◽  
Peter P. Rainer
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Cyclic Gmp ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Dna Sensor ◽  
Sting Pathway

Inflammation plays a central role in cardiovascular diseases (CVD). One pathway under investigation is the innate immune DNA sensor cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING). cGAS-STING upregulates type I interferons in response to pathogens. Recent studies show that also self-DNA may activate cGAS-STING, for instance, DNA released from nuclei or mitochondria during obesity or myocardial infarction. Here, we focus on emerging evidence describing the interaction of cGAS-STING with cardiovascular risk factors and disease. We also touch on translational therapeutic opportunities and potential further investigations.

scholarly journals The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion

2021 ◽  
Vol 12 ◽  
Author(s):  
Tongyu Hu ◽  
Mingyu Pan ◽  
Yue Yin ◽  
Chen Wang ◽  
Ye Cui ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cyclic Gmp ◽  
Mammalian Cells ◽  
Type I Interferon ◽  
Viral Proteins ◽  
Current Status ◽  
Type I ◽  
Non Coding Rnas ◽  
Sting Pathway ◽  
Viral Evasion

Virus infection has been consistently threatening public health. The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. cGAS recognizes the pathogenic DNA in the cytosol and then synthesizes 2′3′-cyclic GMP-AMP (2′3′cGAMP). As the second messenger, cGAMP activates STING and induces the following cascade to produce type I interferon (IFN-I) to protect against infections. However, viruses have evolved numerous strategies to hinder the cGAS-STING signal transduction, promoting their immune evasion. Here we outline the current status of the viral evasion mechanism underlying the regulation of the cGAS-STING pathway, focusing on how post-transcriptional modifications, viral proteins, and non-coding RNAs involve innate immunity during viral infection, attempting to inspire new targets discovery and uncover potential clinical antiviral treatments.

scholarly journals Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

Science ◽  
2012 ◽  
Vol 339 (6121) ◽  
pp. 786-791 ◽  
Author(s):  
L. Sun ◽  
J. Wu ◽  
F. Du ◽  
X. Chen ◽  
Z. J. Chen
Keyword(s):  
Cyclic Gmp ◽  
Type I Interferon ◽  
Type I ◽  
Dna Sensor ◽  
Interferon Pathway
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