Journal
FASEB JOURNAL
Volume 32, Issue 6, Pages 3301-3320Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201700619R
Keywords
mucus; O-glycosylation; N-glycosylation; immune system
Categories
Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)
- BBSRC Institute Strategic Programme for The Gut Health and Food Safety [BB/J004529/1]
- Institute of Food Research (IFR) Strategy Fund Grant
- BBSRC Responsive Mode Grant [BB/K019554/1]
- Biotechnology and Biological Sciences Research Council [BBS/E/F/00044504, BBS/E/F/00044452, BBS/E/F/000PR10356, BBS/E/F/000PR10355, BBS/E/F/000PR10353, BBS/E/F/00042548, BB/K019554/1] Funding Source: researchfish
- BBSRC [BBS/E/F/000PR10355, BBS/E/F/000PR10356, BBS/E/F/00042548, BBS/E/F/00044504, BBS/E/F/00044452, BBS/E/F/000PR10353, BB/K019554/1] Funding Source: UKRI
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Intestinal mucins trigger immune responses upon recognition by dendritic cells via protein-carbohydrate interactions. We used a combination of structural, biochemical, biophysical, and cell-based approaches to decipher the specificity of the interaction between mucin glycans and mammalian lectins expressed in the gut, including galectin (Gal)-3 and C-type lectin receptors. Gal-3 differentially recognized intestinal mucins with different O-glycosylation profiles, as determined by mass spectrometry (MS). Modification of mucin glycosylation, via chemical treatment leading to a loss of terminal glycans, promoted the interaction of Gal-3 to poly-N-acetyllactosamine. Specific interactions were observed between mucins and mouse dendritic cell-associated lectin (mDectin)-2 or specific intercellular adhesion molecule-grabbing nonintegrin-related-1 (SIGN-R1), but not mDectin-1, using a cell-reporter assay, as also confirmed by atomic force spectroscopy. We characterized the N-glycosylation profile of mouse colonic mucin (Muc)-2 by MS and showed that the interaction with mDectin-2 was mediated by high-mannose N-glycans. Furthermore, we observed Gal-3 binding to the 3 C-type lectins by force spectroscopy. We showed that mDectin-1, mDectin-2, and SIGN-R1 are decorated by N-glycan structures that can be recognized by the carbohydrate recognition domain of Gal-3. These findings provide a structural basis for the role of mucins in mediating immune responses and new insights into the structure and function of major mammalian lectins.
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