Golgi anchoring of glycosyltransferases by Fam3 regulators ensures intestinal homeostasis

Golgi anchoring of glycosyltransferases by Fam3 regulators ensures intestinal homeostasis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Golgi anchoring of glycosyltransferases by Fam3 regulators ensures intestinal homeostasis Kiyoshi Takeda, Yuki Ito, Ryu Okumura, Airi Ishibashi, Kei Sakaki, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8837940/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Glycan modification is essential for various physiological processes and depends on precise Golgi localization of glycosyltransferases, yet the underlying mechanisms remain unclear. Here, we show that Fam3b and Fam3d associate with glycosyltransferases Fut2 and B3gnt3, respectively, to ensure Golgi localization. Loss of Fam3b impaired Fut2 localization, leading to proteasomal degradation and loss of α1,2-fucosylation of colonic mucins. Similarly, Fam3d was required for B3gnt3 localization. An N-terminal α-helical domain of Fam3 proteins was identified as a Golgi-localization signal. Both Fam3b-/- and Fam3d-/- mice showed increased susceptibility to dextran sulfate sodium–induced colitis, and reduced FAM3B expression was observed in colonic epithelial cells of ulcerative colitis patients. These findings reveal a previously unrecognized mechanism regulating glycosyltransferase localization and highlight auxiliary regulators of glycosylation as potential therapeutic targets. Biological sciences/Molecular biology/Post-translational modifications/Glycosylation Biological sciences/Molecular biology/Proteomics/Protein–protein interaction networks Biological sciences/Cell biology/Glycobiology Health sciences/Diseases/Immunological disorders/Inflammatory diseases FAM3 family members Fut2 B3gnt3 B3gnt6 inflammatory bowel disease Full Text Additional Declarations There is NO Competing Interest. Supplementary Files nrreportingsummary.pdf Reporting Summary Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8837940","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":590367901,"identity":"1f31feed-2a76-4208-a0ed-ab0f155dea2a","order_by":0,"name":"Kiyoshi 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