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Molecular basis for intestinal mucin recognition by galectin‐3 and C‐type lectins
Author(s) -
Leclaire Charlotte,
Lecointe Karine,
Gunning Patrick A.,
Tribolo Sandra,
Kavanaugh Devon W.,
Wittmann Alexandra,
Latousakis Dimitrios,
MacKenzie Donald A.,
Kawasaki Norihito,
Juge Nathalie
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700619r
Subject(s) - mucin , glycosylation , lectin , glycan , glycoprotein , galectin , dc sign , c type lectin , chemistry , muc1 , microbiology and biotechnology , immune system , biochemistry , biology , dendritic cell , immunology
ABSTRACT 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.—Leclaire, C., Lecointe, K., Gunning, P. A., Tribolo, S., Kavanaugh, D. W., Wittmann, A., Latousakis, D., MacKenzie, D. A., Kawasaki, N., Juge, N. Molecular basis for intestinal mucin recognition by galectin‐3 and C‐type lectins. FASEB J. 32, 3301–3320 (2018). www.fasebj.org