{"doi":"10.1101/2020.02.13.948273","title":"The LRRC8A:C Heteromeric Channel Is a cGAMP Transporter and the Dominant cGAMP Importer in Human Vasculature Cells","abstract":"SUMMARY Extracellular 2’3’-cyclic-GMP-AMP (cGAMP) is an immunotransmitter secreted by cancer cells and taken up by host cells to activate the anti-cancer STING pathway. No cGAMP exporter has been identified, and SLC19A1, a recently identified cGAMP importer, does not account for the import activity in most cell types. Here, we identify the LRRC8A:C heteromeric channel, a volume-regulated anion channel (VRAC), as a cGAMP transporter. This channel mediates cGAMP import or export depending on the cGAMP chemical gradient, and channel activation or inhibition modulates cGAMP transport. Other 2’3’-cyclic dinucleotides are also transported by LRRC8A:C channels, including the investigational cancer therapeutic ADU-S100. Furthermore, we demonstrate that the LRRC8A-containing channel is the dominant cGAMP importer in primary human vasculature cells. Given tumor vasculature’s regulation of immune infiltration and its disruption in response to STING agonists, we have uncovered a leading molecular mechanism for extracellular cGAMP signaling in this important anti-cancer target.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120248,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":252622,"name":"Xianlan Wen","orcid":null,"position":1,"is_corresponding":false},{"id":252621,"name":"Rachel E. Mardjuki","orcid":null,"position":2,"is_corresponding":false},{"id":232617,"name":"Volker Böhnert","orcid":"0000-0002-3205-827X","position":3,"is_corresponding":false},{"id":62605,"name":"Gaelen T. Hess","orcid":"0000-0002-3836-0277","position":4,"is_corresponding":false},{"id":249301,"name":"Christopher Ritchie","orcid":"0000-0001-9432-8602","position":5,"is_corresponding":false},{"id":232616,"name":"Jacqueline A. Carozza","orcid":"0000-0001-6068-2259","position":6,"is_corresponding":false},{"id":249302,"name":"Merritt Maduke","orcid":"0000-0001-7787-306X","position":7,"is_corresponding":false},{"id":62612,"name":"Michael C. Bassik","orcid":"0000-0001-5185-8427","position":8,"is_corresponding":false},{"id":232622,"name":"Lingyin Li","orcid":"0000-0003-4386-7926","position":9,"is_corresponding":false},{"id":249300,"name":"Lauren J. Lahey","orcid":"0000-0003-0026-6864","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-18T23:14:33.640077Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}