{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:45:45Z","timestamp":1780505145982,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M740518"],"award-info":[{"award-number":["2023M740518"]}],"id":[{"id":"10.13039\/501100002858","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":[[2024,2,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease that could cause blindness. It has been established that Norrin forms dimers to activate \u03b2\u2010catenin signaling, yet the core interface for Norrin dimerization and the precise mechanism by which Norrin dimerization contributes to the pathogenesis of FEVR remain elusive. Here, we report an\n                    <jats:italic>NDP<\/jats:italic>\n                    variant, c.265T&gt;C (p.Phe89Leu), that interrupted \u03b2\u2010catenin signaling by disrupting Norrin dimerization. Structural and functional analysis revealed that the Phe\u201089 of one Norrin monomer interacts with Pro\u201098, Ser\u2010101, Arg\u2010121, and Ile\u2010123 of another, forming two core symmetrical dimerization interfaces that are pivotal for the formation of a \u201chand\u2010by\u2010arm\u201d dimer. Intriguingly, we proved that one of the two core symmetrical interfaces is sufficient for dimerization and activation of \u03b2\u2010catenin signaling, with a substantial contribution from the Phe\u201089\/Pro\u201098 interaction. Further functional analysis revealed that the disruption of both dimeric interfaces eliminates potential binding sites for LRP5, which could be partially restored by over\u2010expression of TSPAN12. In conclusion, our findings unveil a core dimerization interface that regulates Norrin\/LRP5 interaction, highlighting the essential role of Norrin dimerization on \u03b2\u2010catenin signaling and providing potential therapeutic avenues for the treatment of FEVR.\n                  <\/jats:p>","DOI":"10.1096\/fj.202302387r","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T11:31:50Z","timestamp":1708083110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deciphering a crucial dimeric interface governing Norrin dimerization and the pathogenesis of familial exudative vitreoretinopathy"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3581-3258","authenticated-orcid":false,"given":"Rulian","family":"Zhao","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, The Department of Medical 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