Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2.
Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2.
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DOI：
10.7554/elife.83037
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发表时间：
2022-12-08
期刊：
影响因子：
7.7
通讯作者：
Yamasaki S
中科院分区：
文献类型：
--
作者：
Haji S;Ito T;Guenther C;Nakano M;Shimizu T;Mori D;Chiba Y;Tanaka M;Mishra SK;Willment JA;Brown GD;Nagae M;Yamasaki S
C型凝集素受体(CLRs)在识别病原体和自身成分上存在的糖结合物后，可诱导免疫反应。虽然Dectin-1是识别病原体上β-葡聚糖的最具特性的CLR，但Dectin-1的内源性靶点还不完全清楚。在此，我们报道人Dectin-1是另一种表达在血小板上的CLEC-2的配体。生化分析表明Dectin-1是一种粘蛋白样蛋白，因为它的茎部高度O-糖基化。人Dectin-1的EDxxT基序上的唾液酸化核心1多聚糖为CLEC-2提供了一个配体部分，这在小鼠Dectin-1中是不存在的。引人注目的是，人Dectin-1在小鼠体内的表达挽救了由于缺乏泊多普宁而导致的致命性和淋巴缺陷。泊多普宁是一种已知的CLEC-2配体。这一发现是先天免疫受体也作为生理配体在糖基化时调节个体发育的第一个例子。
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.
影响因子：
3.1
作者：
Ozaki Y;Tamura S;Suzuki-Inoue K
通讯作者：
Suzuki-Inoue K