{"doi":"10.1126/sciadv.ado7024","title":"2′3′-cGAMP interactome identifies 2′3′-cGAMP/Rab18/FosB signaling in cell migration control independent of innate immunity","abstract":"c-di-GAMP was first identified in bacteria to promote colonization, while mammalian 2′3′-cGAMP is synthesized by cGAS to activate STING for innate immune stimulation. However, 2′3′-cGAMP function beyond innate immunity remains elusive. Here, we report that 2′3′-cGAMP promotes cell migration independent of innate immunity. 2′3′-cGAMP interactome analysis identifies the small GTPase Rab18 as a 2′3′-cGAMP binding partner and effector in cell migration control. Mechanistically, 2′3′-cGAMP binds Rab18 to facilitate GTP loading and subsequent Rab18 activation, which further promotes FosB transcription in facilitating cell migration. Induced synthesis of endogenous 2′3′-cGAMP by intrabreast tumor bacterium S. aureus infection or low-dose doxorubicin treatment facilitates cell migration depending on the cGAS/cGAMP/Rab18/FosB signaling. We find that lovastatin induces Rab18 deprenylation that abolishes 2′3′-cGAMP recognition therefore suppressing cell migration. Together, our study reveals a previously unidentified 2′3′-cGAMP function in cell migration control via the 2′3′-cGAMP/Rab18/FosB signaling that provides additional insights into clinical applications of 2′3′-cGAMP.","journal":"Science Advances","year":2024,"id":443464,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1018423,"name":"Quentin Hahn","orcid":"0000-0003-3510-8364","position":1,"is_corresponding":false},{"id":593433,"name":"Le Yu","orcid":"0000-0002-5898-8088","position":2,"is_corresponding":false},{"id":484229,"name":"Zhichuan Zhu","orcid":"0000-0003-0327-9978","position":3,"is_corresponding":false},{"id":484227,"name":"Joshua A. 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