{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:10:05Z","timestamp":1781716205243,"version":"3.54.5"},"reference-count":52,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY021731"],"award-info":[{"award-number":["R01EY021731"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY011373"],"award-info":[{"award-number":["P30EY011373"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1RR024989"],"award-info":[{"award-number":["UL1RR024989"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A K296E mutation in rhodopsin causes autosomal dominant retinitis pigmentosa, a progressive retinal degenerative disease. Early characterizations of this mutation indicated that it causes the receptor to be constitutively active, which has been the primary focus when considering the pathogenic mechanism of the mutation thus far. Knockin mice expressing the K296E rhodopsin mutant were generated and characterized to better understand the pathogenic mechanism of the mutation. Knockin mice exhibited progressive retinal degeneration characteristic of retinitis pigmentosa. The K296E rhodopsin mutant mislocalized in photoreceptor cells and, surprisingly, appeared to aggregate, as indicated by the dye PROTEOSTAT, which binds protein aggregates. The propensity of the K296E rhodopsin mutant to aggregate was tested and confirmed in\u00a0vitro but was dependent on the species background of rhodopsin. The K296E mutation on either murine or human rhodopsin backgrounds exhibited similar propensities to aggregate. The same mutation on a bovine rhodopsin background, however, exhibited a lower propensity to aggregate, indicating this species background does not adequately model the effects of the K296E mutation. In contrast to previous expectations, we demonstrate here that aggregation of the K296E rhodopsin mutant may contribute to photoreceptor cell loss in retinitis pigmentosa.<\/jats:p>","DOI":"10.1096\/fj.202501043r","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T03:25:12Z","timestamp":1752722712000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aggregation of the Constitutively Active\n                    <scp>K296E<\/scp>\n                    Rhodopsin Mutant Contributes to Retinal Degeneration"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9534-4559","authenticated-orcid":false,"given":"Sreelakshmi","family":"Vasudevan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-4994","authenticated-orcid":false,"given":"Vivek","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-9693","authenticated-orcid":false,"given":"Paul S.\u2010H.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.08.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69740-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.10.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.11.015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(96)00021-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/343364a0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45748-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417197-8.00001-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(91)90119-Y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.78.5.353"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90034-B"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3212-06.2006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3551"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1402"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10222"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.14.2907"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2018.08.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05449.2001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2018.03.030"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00272a020"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15979"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-025-02311-4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.08.042"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.06.004"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.0c00733"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.209759"},{"key":"e_1_2_9_31_1","first-page":"295","article-title":"Analysis of ERG a\u2010Wave Amplification and Kinetics in Terms of the G\u2010Protein Cascade of Phototransduction","volume":"35","author":"Breton M. E.","year":"1994","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_9_32_1","first-page":"2070","article-title":"The A\u2010Wave of the Human Electroretinogram and Rod Receptor Function","volume":"31","author":"Hood D. C.","year":"1990","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2007.09.003"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(86)90017-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8669-9_19"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-010-9138-4"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.3.880"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/367639a0"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042133"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0516273"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1738"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-021-02522-5"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2016.04.013"},{"key":"e_1_2_9_44_1","first-page":"1149","article-title":"A Novel Rhodopsin Mutation at the Retinal Binding Site (Lys\u2010296\u2010Met) in ADRP","volume":"34","author":"Sullivan J. M.","year":"1993","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13559"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00037a035"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00186a011"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi101345x"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19890"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14010049"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-022-01735-y"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010417117"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210678109"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202501043R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:10:16Z","timestamp":1761693016000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202501043R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":52,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2025,7,31]]}},"alternative-id":["10.1096\/fj.202501043R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202501043r","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.26.643112","asserted-by":"object"}]},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,16]]},"assertion":[{"value":"2025-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70848"}}