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Here, we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-\u03baB and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations in OPTN linked to primary open-angle glaucoma (POAG) cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. By using proximity labelling proteomics, we identify the linear ubiquitin assembly complex (LUBAC), CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-\u03baB and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment, leading to altered pro-inflammatory cytokine secretion.<\/jats:p>","DOI":"10.1242\/jcs.239822","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T20:45:41Z","timestamp":1588797941000},"source":"Crossref","is-referenced-by-count":38,"title":["OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion"],"prefix":"10.1242","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-2352","authenticated-orcid":false,"given":"Thomas","family":"O'Loughlin","sequence":"first","affiliation":[{"name":"Cambridge Institute for Medical Research 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"},{"name":"University of Cambridge 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"},{"name":"Helen Diller Family Comprehensive Cancer Center 2 , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina J.","family":"Kruppa","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"},{"name":"University of Cambridge 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre L. R.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Eastman Dental Institute, University College London 3 Microbial Diseases , , London WC1X 8LD , UK"},{"name":"University Centre of Par\u00e1 4 Department of Oral and Maxillofacial Surgery , , Bel\u00e9m , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Edgar","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"},{"name":"University of Cambridge 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Ghannam","sequence":"additional","affiliation":[{"name":"Eastman Dental Institute, University College London 3 Microbial Diseases , , London WC1X 8LD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Eastman Dental Institute, University College London 3 Microbial Diseases , , London WC1X 8LD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4457-3479","authenticated-orcid":false,"given":"Folma","family":"Buss","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"},{"name":"University of Cambridge 1 , The Keith Peters Building , , Hills Road, Cambridge CB2 0XY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2024061318514821500_JCS239822C1","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/ng.562","article-title":"Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone","volume":"42","author":"Albagha","year":"2010","journal-title":"Nat. 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