Enzymes
UniProtKB help_outline | 211 proteins |
Reaction participants Show >> << Hide
- Name help_outline 2',3'-cGAMP Identifier CHEBI:143093 Charge -2 Formula C20H22N10O13P2 InChIKeyhelp_outline XRILCFTWUCUKJR-INFSMZHSSA-L SMILEShelp_outline P1(O[C@@H]2[C@H](O[C@H]([C@@H]2O)N3C=NC=4C(=NC=NC43)N)COP(=O)(O[C@H]5[C@@H](O[C@@H]([C@H]5O)CO1)N6C=NC=7C(NC(=NC76)N)=O)[O-])(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 9 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:66320 | RHEA:66321 | RHEA:66322 | RHEA:66323 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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Publications
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Transfer of cgamp into bystander cells via LRRC8 volume-regulated anion channels augments STING-mediated interferon responses and anti-viral immunity.
Zhou C., Chen X., Planells-Cases R., Chu J., Wang L., Cao L., Li Z., Lopez-Cayuqueo K.I., Xie Y., Ye S., Wang X., Ullrich F., Ma S., Fang Y., Zhang X., Qian Z., Liang X., Cai S.Q., Jiang Z., Zhou D., Leng Q., Xiao T.S., Lan K., Yang J., Li H., Peng C., Qiu Z., Jentsch T.J., Xiao H.
The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA in infected and malignant cells and catalyzes the formation of 2'3'cGMP-AMP (cGAMP), which in turn triggers interferon (IFN) production via the STING pathway. Here, we examined the contribution of anion channels to cGAMP transfer and a ... >> More
The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA in infected and malignant cells and catalyzes the formation of 2'3'cGMP-AMP (cGAMP), which in turn triggers interferon (IFN) production via the STING pathway. Here, we examined the contribution of anion channels to cGAMP transfer and anti-viral defense. A candidate screen revealed that inhibition of volume-regulated anion channels (VRACs) increased propagation of the DNA virus HSV-1 but not the RNA virus VSV. Chemical blockade or genetic ablation of LRRC8A/SWELL1, a VRAC subunit, resulted in defective IFN responses to HSV-1. Biochemical and electrophysiological analyses revealed that LRRC8A/LRRC8E-containing VRACs transport cGAMP and cyclic dinucleotides across the plasma membrane. Enhancing VRAC activity by hypotonic cell swelling, cisplatin, GTPĪ³S, or the cytokines TNF or interleukin-1 increased STING-dependent IFN response to extracellular but not intracellular cGAMP. Lrrc8e<sup>-/-</sup> mice exhibited impaired IFN responses and compromised immunity to HSV-1. Our findings suggest that cell-to-cell transmission of cGAMP via LRRC8/VRAC channels is central to effective anti-viral immunity. << Less
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LRRC8A:C/E heteromeric channels are ubiquitous transporters of cGAMP.
Lahey L.J., Mardjuki R.E., Wen X., Hess G.T., Ritchie C., Carozza J.A., Boehnert V., Maduke M., Bassik M.C., Li L.
Extracellular 2'3'-cyclic-GMP-AMP (cGAMP) is an immunotransmitter exported by diseased cells and imported into host cells to activate the innate immune STING pathway. We previously identified SLC19A1 as a cGAMP importer, but its use across human cell lines is limited. Here, we identify LRRC8A hete ... >> More
Extracellular 2'3'-cyclic-GMP-AMP (cGAMP) is an immunotransmitter exported by diseased cells and imported into host cells to activate the innate immune STING pathway. We previously identified SLC19A1 as a cGAMP importer, but its use across human cell lines is limited. Here, we identify LRRC8A heteromeric channels, better known as volume-regulated anion channels (VRAC), as widely expressed cGAMP transporters. LRRC8A forms complexes with LRRC8C and/or LRRC8E, depending on their expression levels, to transport cGAMP and other 2'3'-cyclic dinucleotides. In contrast, LRRC8D inhibits cGAMP transport. We demonstrate that cGAMP is effluxed or influxed via LRRC8 channels, as dictated by the cGAMP electrochemical gradient. Activation of LRRC8A channels, which can occur under diverse stresses, strongly potentiates cGAMP transport. We identify activator sphingosine 1-phosphate and inhibitor DCPIB as chemical tools to manipulate channel-mediated cGAMP transport. Finally, LRRC8A channels are key cGAMP transporters in resting primary human vasculature cells and universal human cGAMP transporters when activated. << Less