Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Mol Cell Proteomics. 2023 Sep;22(9):100615. doi: 10.1016/j.mcpro.2023.100615. Epub 2023 Jul 4.
The asialoglycoprotein receptor (ASGPR) and the mannose receptor C-type 1 (MRC1) are well known for their selective recognition and clearance of circulating glycoproteins. Terminal galactose and N-Acetylgalactosamine are recognized by ASGPR, while terminal mannose, fucose, and N-Acetylglucosamine are recognized by MRC1. The effects of ASGPR and MRC1 deficiency on the N-glycosylation of individual circulating proteins have been studied. However, the impact on the homeostasis of the major plasma glycoproteins is debated and their glycosylation has not been mapped with high molecular resolution in this context. Therefore, we evaluated the total plasma N-glycome and plasma proteome of ASGR1 and MRC1 deficient mice. ASGPR deficiency resulted in an increase in O-acetylation of sialic acids accompanied by higher levels of apolipoprotein D, haptoglobin, and vitronectin. MRC1 deficiency decreased fucosylation without affecting the abundance of the major circulating glycoproteins. Our findings confirm that concentrations and N-glycosylation of the major plasma proteins are tightly controlled and further suggest that glycan-binding receptors have redundancy, allowing compensation for the loss of one major clearance receptor.
去唾液酸糖蛋白受体 (ASGPR) 和甘露糖受体 C 型 1 (MRC1) 以其对循环糖蛋白的选择性识别和清除而闻名。ASGPR 识别末端半乳糖和 N-乙酰半乳糖胺，而 MRC1 识别末端甘露糖、岩藻糖和 N-乙酰葡萄糖胺。已经研究了 ASGPR 和 MRC1 缺乏对个体循环蛋白 N-糖基化的影响。然而，关于其对主要血浆糖蛋白的动态平衡的影响存在争议，并且在这种情况下尚未以高分子分辨率对其糖基化进行映射。因此，我们评估了 ASGR1 和 MRC1 缺乏小鼠的总血浆 N-糖组和血浆蛋白质组。ASGPR 缺乏导致唾液酸的 O-乙酰化增加，同时载脂蛋白 D、触珠蛋白和 vitronectin 的水平升高。MRC1 缺乏导致岩藻糖基化减少，但不影响主要循环糖蛋白的丰度。我们的发现证实了主要血浆蛋白的浓度和 N-糖基化受到严格控制，并进一步表明聚糖结合受体具有冗余性，允许对一种主要清除受体的丧失进行补偿。
