{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:39:26Z","timestamp":1787312366241,"version":"build-2736575974"},"reference-count":66,"publisher":"Society for Neuroscience","issue":"48","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":221,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["21H02657"],"award-info":[{"award-number":["21H02657"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["24K09996"],"award-info":[{"award-number":["24K09996"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["23K18199"],"award-info":[{"award-number":["23K18199"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21gm1510006"],"award-info":[{"award-number":["21gm1510006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MEXT | Japan Science and Technology Agency","award":["JPMJMS2024"],"award-info":[{"award-number":["JPMJMS2024"]}]},{"name":"MEXT | Japan Science and Technology Agency","award":["JPMJPF2018"],"award-info":[{"award-number":["JPMJPF2018"]}]},{"DOI":"10.13039\/501100004206","name":"Osaka University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jneurosci.org"],"crossmark-restriction":true},"short-container-title":["J. Neurosci."],"accepted":{"date-parts":[[2025,10,13]]},"published-print":{"date-parts":[[2025,11,26]]},"abstract":"<jats:p>\n                    Transducin is a heterotrimeric G-protein that is a component of the phototransduction cascade in rod and cone photoreceptor cells of the retina. Gnat1, a rod-specific transducin \u03b1-subunit, regulates light\/dark adaptation by changing its subcellular localization depending on light. Our previous study revealed that Gnat1 translocation in rod photoreceptor cells under light\/dark conditions requires E3 ligase Klhl18-mediated ubiquitination and degradation of Unc119, a Gnat1-binding protein. A mutation in the human\n                    <jats:italic>UNC119<\/jats:italic>\n                    gene is associated with cone\u2013rod dystrophy (CRD); however, the underlying pathological mechanism remains unclear. In this study, we generated and analyzed\n                    <jats:italic>Unc119<\/jats:italic>\n                    -deficient (\n                    <jats:italic>\n                      Unc119\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice. We found that the retinas of\n                    <jats:italic>\n                      Unc119\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice of both sexes exhibited progressive photoreceptor degeneration, resembling CRD in humans. We also found that Unc119 interacts with Gnat2 in cone photoreceptor cells and that Unc119 is essential for the translocation of Gnat2 to the outer segment in cone photoreceptor cells. RNA-seq and subsequent bioinformatics analysis revealed the predicted activation of the JAK-STAT and NF-\u03baB pathways in the\n                    <jats:italic>\n                      Unc119\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    retina. Treatment of\n                    <jats:italic>\n                      Unc119\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice with curcumin, an inhibitor of the JAK-STAT and NF-\u03baB pathways, suppressed inflammation and cone photoreceptor cell degeneration in\n                    <jats:italic>\n                      Unc119\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    retinas. Furthermore, a human CRD-associated\n                    <jats:italic>UNC119<\/jats:italic>\n                    mutant protein competitively inhibited the interaction between UNC119 and GNAT1 or GNAT2. Taken together, the current study suggests that UNC119 dysfunction leads to CRD by affecting the JAK-STAT and NF-\u03baB pathways and may advance our understanding of the pathological mechanisms of CRD.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2245-24.2025","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:55:14Z","timestamp":1760723714000},"page":"e2245242025","update-policy":"https:\/\/doi.org\/10.1523\/jneurosci.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Dysfunction of Unc119, a Transducin-Binding Protein, Leads to Cone\u2013Rod Dystrophy through Activating JAK-Stat and NF-\u03baB Inflammatory Pathways in the Mouse Retina"],"prefix":"10.1523","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5936-6229","authenticated-orcid":false,"given":"Koki","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5562-8733","authenticated-orcid":false,"given":"Taro","family":"Chaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Ya","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamato","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryotaro","family":"Tsutsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Tsujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Okuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4171-220X","authenticated-orcid":false,"given":"Takahisa","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"2025120910400678000_45.48.e2245242025.1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/ptr.6642","article-title":"Potential therapeutic effects of curcumin mediated by JAK\/STAT signaling pathway: a review","volume":"34","author":"Ashrafizadeh","year":"2020","journal-title":"Phytother Res"},{"key":"2025120910400678000_45.48.e2245242025.2","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1038\/s41598-018-22096-0","article-title":"Clinical and genetic characteristics of 251 consecutive patients with macular and cone\/cone-rod dystrophy","volume":"8","author":"Birtel","year":"2018","journal-title":"Sci Rep"},{"key":"2025120910400678000_45.48.e2245242025.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058023"},{"key":"2025120910400678000_45.48.e2245242025.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.3101175"},{"key":"2025120910400678000_45.48.e2245242025.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250478897"},{"key":"2025120910400678000_45.48.e2245242025.6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00058"},{"key":"2025120910400678000_45.48.e2245242025.7","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2015-306939"},{"key":"2025120910400678000_45.48.e2245242025.8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-8-74"},{"key":"2025120910400678000_45.48.e2245242025.9","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1468"},{"key":"2025120910400678000_45.48.e2245242025.10","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101409"},{"key":"2025120910400678000_45.48.e2245242025.11","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab268"},{"key":"2025120910400678000_45.48.e2245242025.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2004.05.002"},{"key":"2025120910400678000_45.48.e2245242025.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"2025120910400678000_45.48.e2245242025.14","doi-asserted-by":"crossref","first-page":"e0168966","DOI":"10.1371\/journal.pone.0168966","article-title":"Novel candidate genes and a wide spectrum of structural and point mutations responsible for inherited retinal dystrophies revealed by exome sequencing","volume":"11","author":"de Castro-Miro","year":"2016","journal-title":"PLoS One"},{"key":"2025120910400678000_45.48.e2245242025.15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s43587-022-00281-1","article-title":"Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer\u2019s disease mouse models","volume":"2","author":"Dejanovic","year":"2022","journal-title":"Nat Aging"},{"key":"2025120910400678000_45.48.e2245242025.16","doi-asserted-by":"crossref","first-page":"8106","DOI":"10.3390\/ijms24098106","article-title":"A novel role for UNC119 as an enhancer of synaptic transmission","volume":"24","author":"Fehlhaber","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025120910400678000_45.48.e2245242025.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.11.001"},{"key":"2025120910400678000_45.48.e2245242025.18","doi-asserted-by":"publisher","DOI":"10.1021\/bi8015444"},{"key":"2025120910400678000_45.48.e2245242025.19","doi-asserted-by":"publisher","DOI":"10.1084\/jem. 20030589"},{"key":"2025120910400678000_45.48.e2245242025.20","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ajo.2023.09.019","article-title":"Drusen and other retinal findings in people with IgA glomerulonephritis","volume":"257","author":"Greferath","year":"2024","journal-title":"Am J Ophthalmol"},{"key":"2025120910400678000_45.48.e2245242025.21","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07128.x"},{"key":"2025120910400678000_45.48.e2245242025.22","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-7"},{"key":"2025120910400678000_45.48.e2245242025.23","first-page":"543","article-title":"Gene therapy for color blindness","volume":"90","author":"Hassall","year":"2017","journal-title":"Yale J Biol Med"},{"key":"2025120910400678000_45.48.e2245242025.24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.3.1797"},{"key":"2025120910400678000_45.48.e2245242025.25","first-page":"690","article-title":"Localization of HRG4, a photoreceptor protein homologous to Unc-119, in ribbon synapse","volume":"39","author":"Higashide","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025120910400678000_45.48.e2245242025.26","first-page":"2767","article-title":"Hyaluronan and the functional organization of the interphotoreceptor matrix","volume":"40","author":"Hollyfield","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025120910400678000_45.48.e2245242025.27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44646"},{"key":"2025120910400678000_45.48.e2245242025.28","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: from bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2025120910400678000_45.48.e2245242025.29","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.3892\/mmr.2013.1415","article-title":"Screening for variants in 20 genes in 130 unrelated patients with cone-rod dystrophy","volume":"7","author":"Huang","year":"2013","journal-title":"Mol Med Rep"},{"key":"2025120910400678000_45.48.e2245242025.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2006.10.016"},{"key":"2025120910400678000_45.48.e2245242025.31","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0278-0"},{"key":"2025120910400678000_45.48.e2245242025.32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2494-07.2007"},{"key":"2025120910400678000_45.48.e2245242025.33","first-page":"3268","article-title":"HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model","volume":"41","author":"Kobayashi","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025120910400678000_45.48.e2245242025.34","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01209-07"},{"key":"2025120910400678000_45.48.e2245242025.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0824-17.2017"},{"key":"2025120910400678000_45.48.e2245242025.36","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8418"},{"key":"2025120910400678000_45.48.e2245242025.37","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-kappaB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"2025120910400678000_45.48.e2245242025.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0613-10.2010"},{"key":"2025120910400678000_45.48.e2245242025.39","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/141.3.977"},{"key":"2025120910400678000_45.48.e2245242025.40","doi-asserted-by":"publisher","DOI":"10.1038\/ng774"},{"key":"2025120910400678000_45.48.e2245242025.41","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13330"},{"key":"2025120910400678000_45.48.e2245242025.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121875119"},{"key":"2025120910400678000_45.48.e2245242025.43","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)81144-4"},{"key":"2025120910400678000_45.48.e2245242025.44","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2401-08.2008"},{"key":"2025120910400678000_45.48.e2245242025.45","first-page":"895","article-title":"Relb, a member of the Rel\/NF-kappa B family of transcription factors","volume":"29","author":"Ryseck","year":"1996","journal-title":"Braz J Med Biol Res"},{"key":"2025120910400678000_45.48.e2245242025.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2012.04.004"},{"key":"2025120910400678000_45.48.e2245242025.47","doi-asserted-by":"publisher","DOI":"10.1007\/BF00741450"},{"key":"2025120910400678000_45.48.e2245242025.48","doi-asserted-by":"crossref","first-page":"586013","DOI":"10.3389\/fnins.2020.586013","article-title":"Influence of aging on the retina and visual motion processing for optokinetic responses in mice","volume":"14","author":"Sugita","year":"2020","journal-title":"Front Neurosci"},{"key":"2025120910400678000_45.48.e2245242025.49","first-page":"2085","article-title":"Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors","volume":"39","author":"Swanson","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025120910400678000_45.48.e2245242025.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.1.266"},{"key":"2025120910400678000_45.48.e2245242025.51","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jneuroim.2016.07.014","article-title":"Complimentary action: C1q increases ganglion cell survival in an in vitro model of retinal degeneration","volume":"298","author":"Taylor","year":"2016","journal-title":"J Neuroimmunol"},{"key":"2025120910400678000_45.48.e2245242025.52","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-95046-4_12"},{"key":"2025120910400678000_45.48.e2245242025.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2018.04.005"},{"key":"2025120910400678000_45.48.e2245242025.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101686"},{"key":"2025120910400678000_45.48.e2245242025.55","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.2741\/4018","article-title":"RHAMM and CD44 peptides-analytic tools and potential drugs","volume":"17","author":"Turley","year":"2012","journal-title":"Front Biosci (Landmark Ed)"},{"key":"2025120910400678000_45.48.e2245242025.56","doi-asserted-by":"crossref","first-page":"109380","DOI":"10.1016\/j.isci.2024.109380","article-title":"The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases","volume":"27","author":"Varner","year":"2024","journal-title":"iScience"},{"key":"2025120910400678000_45.48.e2245242025.57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005211"},{"key":"2025120910400678000_45.48.e2245242025.58","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1080\/08923973.2018.1469145","article-title":"Curcumin as a therapeutic agent for blocking NF-kappaB activation in ulcerative colitis","volume":"40","author":"Wang","year":"2018","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"2025120910400678000_45.48.e2245242025.59","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0089-15.2015"},{"key":"2025120910400678000_45.48.e2245242025.60","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490200216"},{"key":"2025120910400678000_45.48.e2245242025.61","first-page":"100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"2025120910400678000_45.48.e2245242025.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.12.072"},{"key":"2025120910400678000_45.48.e2245242025.63","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s40942-022-00431-y","article-title":"C1q and the classical complement cascade in geographic atrophy secondary to age-related macular degeneration","volume":"8","author":"Yednock","year":"2022","journal-title":"Int J Retina Vitreous"},{"key":"2025120910400678000_45.48.e2245242025.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105461"},{"key":"2025120910400678000_45.48.e2245242025.65","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00417-022-05786-4","article-title":"Clinical-genetic findings in a group of subjects with macular dystrophies due to mutations in rare inherited retinopathy genes","volume":"261","author":"Zenteno","year":"2023","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2025120910400678000_45.48.e2245242025.66","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2835"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2245-24.2025","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2245-24.2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T18:40:42Z","timestamp":1765305642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2245-24.2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":66,"journal-issue":{"issue":"48","published-online":{"date-parts":[[2025,11,26]]},"published-print":{"date-parts":[[2025,11,26]]}},"alternative-id":["10.1523\/JNEUROSCI.2245-24.2025"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2245-24.2025","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]}}}