Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

Archive ouverte

Haji, Shojiro | Ito, Taiki | Guenther, Carla | Nakano, Miyako | Shimizu, Takashi | Mori, Daiki | Chiba, Yasunori | Tanaka, Masato | Mishra, Sushil, K | Willment, Janet, A | Brown, Gordon, D | Nagae, Masamichi | Yamasaki, Sho

Edité par CCSD ; eLife Sciences Publication -

International audience. C-type lectin receptors (CLRs) elicit immune responses upon recognition of glycoconjugates present on pathogens and self-components. While Dectin-1 is the best-characterized CLR recognizing β-glucan on pathogens, the endogenous targets of Dectin-1 are not fully understood. Herein, we report that human Dectin-1 is a ligand for CLEC-2, another CLR expressed on platelets. Biochemical analyses revealed that Dectin-1 is a mucin-like protein as its stalk region is highly O -glycosylated. A sialylated core 1 glycan attached to the EDxxT motif of human Dectin-1, which is absent in mouse Dectin-1, provides a ligand moiety for CLEC-2. Strikingly, the expression of human Dectin-1 in mice rescued the lethality and lymphatic defect resulting from a deficiency of Podoplanin, a known CLEC-2 ligand. This finding is the first example of an innate immune receptor also functioning as a physiological ligand to regulate ontogeny upon glycosylation.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion