Loss of core fucosylation of low-density lipoprotein receptor-related protein-1 impairs its function, leading to the upregulation of serum levels of insulin-like growth factor-binding protein 3 in Fut8-/- mice
Loss of core fucosylation of low-density lipoprotein receptor-related protein-1 impairs its function, leading to the upregulation of serum levels of insulin-like growth factor-binding protein 3 in Fut8-/- mice
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DOI：
10.1093/jb/mvj039
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发表时间：
2006-03-01
影响因子：
2.7
通讯作者：
Taniguchi, N
中科院分区：
文献类型：
--
作者：
Lee, SH;Takahashi, M;Taniguchi, N
α-1，6-岩藻糖基转移酶(Fut8)催化将岩藻糖残基从GDP-岩藻糖转移到N-糖链最内侧的N-乙酰氨基葡萄糖残基。在此，我们报道了核心岩藻糖基化的缺失损害了多功能清道夫和信号受体低密度脂蛋白受体相关蛋白-1(LRP-1)的功能，导致Fut8基因缺失(Fut8(-/-))小鼠来源的细胞内吞胰岛素样生长因子(IGF)结合蛋白-3(IGFBP-3)的能力降低。通过重新引入Fut8，减少的内吞作用得以恢复。Fut8(-/-)小鼠血清IGFBP-3水平明显升高。这些数据清楚地表明，核心岩藻糖基化对LRP-1在体内的清除活性至关重要。
alpha 1,6-Fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue from GDP-fucose to the innermost N-acetylglucosamine residue of N-glycans. Here we report that the loss of core fucosylation impairs the function of low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1), a multifunctional scavenger and signaling receptor, resulting in a reduction in the endocytosis of insulin like growth factor (IGF)-binding protein-3 (IGFBP-3) in the cells derived from Fut8-null (Fut8(-/-)) mice. The reduced endocytosis was restored by the re-introduction of Fut8. Serum levels of IGFBP-3 were markedly upregulated in Fut8(-/-) mice. These data clearly indicate that core fucosylation is crucial for the scavenging activity of LRP-1 in vivo.