{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lahey LJ"],"funding":["NICHD NIH HHS","U.S. Department of Defense","NCI NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["578-591.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12629894"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["80(4)"],"pubmed_abstract":["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, strong"],"journal":["Molecular cell"],"pubmed_title":["LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP."],"pmcid":["PMC12629894"],"funding_grant_id":["T32 GM120007","DP2 HD084069","DP2 CA228044"],"pubmed_authors":["Wen X","Carozza JA","Maduke M","Lahey LJ","Hess GT","Bohnert V","Ritchie C","Mardjuki RE","Bassik MC","Li L"],"additional_accession":[]},"is_claimable":false,"name":"LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP.","description":"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, strong","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2026-05-19T03:18:55.068Z","creation":"2026-05-19T03:11:56.841Z"},"accession":"S-EPMC12629894","cross_references":{"pubmed":["33171122"],"doi":["10.1016/j.molcel.2020.10.021"]}}