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Glycoconjugates undergo endocytic trafficking. According to the glycolipid-lectin (GL-Lect) hypothesis, the construction of tubular endocytic pits is driven in a glycosphingolipid-dependent manner by sugar-binding proteins of the galectin family. Here, we provide evidence for a function of the GL-Lect mechanism in transcytosis across enterocytes in the mouse intestine. We show that galectin-3 (Gal3) and its newly identified binding partner lactotransferrin are transported in a glycosphingolipid-dependent manner from the apical to the basolateral membrane. Transcytosis of lactotransferrin is perturbed in Gal3 knockout mice and can be rescued by exogenous Gal3. Inside enterocytes, Gal3 is localized to hallmark structures of the GL-Lect mechanism, termed clathrin-independent carriers. These data pioneer the existence of GL-Lect endocytosis in vivo and strongly suggest that polarized trafficking across the intestinal barrier relies on this mechanism.<\/jats:p>","DOI":"10.1038\/s42003-021-01693-2","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T16:23:32Z","timestamp":1612887812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Glycolipid-dependent and lectin-driven transcytosis in mouse enterocytes"],"prefix":"10.1038","volume":"4","author":[{"given":"Alena","family":"Ivashenka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9091-0080","authenticated-orcid":false,"given":"Christian","family":"Wunder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Chambon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-9458","authenticated-orcid":false,"given":"Roger","family":"Sandhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Jennemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Dransart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Podsypanina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-3662","authenticated-orcid":false,"given":"B\u00e9rang\u00e8re","family":"Lombard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-8842","authenticated-orcid":false,"given":"Damarys","family":"Loew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5430-2707","authenticated-orcid":false,"given":"Christophe","family":"Lamaze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Poirier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann-Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-0004","authenticated-orcid":false,"given":"Ludger","family":"Johannes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7582-8131","authenticated-orcid":false,"given":"Massiullah","family":"Shafaq-Zadah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"1693_CR1","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1111\/tra.12335","volume":"16","author":"MS Robinson","year":"2015","unstructured":"Robinson, M. 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