Cell surface counter receptors are essential components of the unconventional export machinery of galectin-1
Cell surface counter receptors are essential components of the unconventional export machinery of galectin-1
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DOI：
10.1083/jcb.200506026
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发表时间：
2005-10-24
影响因子：
7.8
通讯作者：
Nickel, W
中科院分区：
文献类型：
--
作者：
Seelenmeyer, C;Wegehingel, S;Nickel, W
半乳糖凝集素-1是细胞外基质的一种成分，也是细胞表面反受体如含β-半乳糖苷的糖脂的配体，然而，半乳糖凝集素-1分泌的分子机制仍然难以捉摸。基于对半乳糖凝集素-1输出突变体的无偏见筛选，我们已经确定了26个单一氨基酸的变化，导致出口和结合到反受体的缺陷。当在CHO克隆13细胞（一种不能表达功能性半乳糖凝集素-1反受体的突变细胞系）中分析野生型半乳糖凝集素-1时，分泌被阻断。有趣的是，我们还发现半乳糖凝集素-1的远亲，真菌凝集素CGL-2，是从中国仓鼠卵巢（CHO）细胞的非经典出口的底物。与哺乳动物半乳糖凝集素-1类似，β-半乳糖苷结合缺陷的CGL-2突变体不能从CHO细胞中输出。我们得出结论，β-半乳糖苷结合位点代表了半乳糖凝集素的主要靶向基序，其定义了半乳糖凝集素输出机制，该机制利用含有β-半乳糖苷的表面分子作为细胞内半乳糖凝集素-1的输出受体。
Galectin-1 is a component of the extracellular matrix as well as a ligand of cell surface counter receptors such as beta-galactoside-containing glycolipids, however, the molecular mechanism of galectin-1 secretion has remained elusive. Based on a nonbiased screen for galectin-1 export mutants we have identified 26 single amino acid changes that cause a defect of both export and binding to counter receptors. When wild-type galectin-1 was analyzed in CHO clone 13 cells, a mutant cell line incapable of expressing functional galectin-1 counter receptors, secretion was blocked. Intriguingly, we also find that a distant relative of galectin-1, the fungal lectin CGL-2, is a substrate for nonclassical export from Chinese hamster ovary (CHO) cells. Alike mammalian galectin-1, a CGL-2 mutant defective in beta-galactoside binding, does not get exported from CHO cells. We conclude that the beta-galactoside binding site represents the primary targeting motif of galectins defining a galectin export machinery that makes use of beta-galactoside-containing surface molecules as export receptors for intracellular galectin-1.