Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site
Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site
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DOI：
10.1083/jcb.138.6.1355
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发表时间：
1997-09-22
影响因子：
7.8
通讯作者：
Filbin, MT
中科院分区：
文献类型：
--
作者：
Tang, S;Shen, YJ;Filbin, MT
髓磷脂中的抑制成分是哺乳动物CNS再生缺乏的主要原因。髓磷脂相关糖蛋白（MAG）是一种唾液酸结合蛋白，是髓磷脂的一种成分，是体内外多种神经元突起生长的有效抑制剂。在这里，我们表明，MAG的唾液酸结合位点是从它的轴突抑制活性不同。单独地，MAG与神经元的唾液酸依赖性结合不足以影响轴突生长的抑制。因此，虽然可溶性MAG-Fc（MAG胞外结构域融合至Fc）、缺失Ig结构域4和5的MAG-Fc的截短形式、MAG（d1-3）-Fc和另一种唾液酸结合蛋白唾液酸粘附素各自以唾液酸依赖性方式结合神经元，但仅全长MAG-Fc抑制神经突生长。这些结果表明，第二个网站上必须存在的MAG，elancements这种反应。与该模型一致，MAG中精氨酸118（R118）突变为丙氨酸或天冬氨酸消除了其唾液酸依赖性结合。然而，当在CHO或Schwann细胞的表面表达时，R118突变的MAG保留了抑制轴突生长的能力。因此，MAG具有两个神经元识别位点，R118处的唾液酸结合位点和前三个IG结构域中不存在的独特抑制位点。
Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid-dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, and another sialic acid binding protein, sialoadhesin, each bind to neurons in a sialic acid-dependent manner, only full-length MAG-Fc inhibits neurite outgrowth. These results suggest that a second site must exist on MAG which elicits this response. Consistent with this model, mutation of arginine 118 (R118) in MAG to either alanine or aspartate abolishes its sialic acid-dependent binding. However, when expressed at the surface of either CHO or Schwann cells, R118-mutated MAG retains the ability to inhibit axonal outgrowth. Hence, MAG has two recognition sites for neurons, the sialic acid binding site at R118 and a distinct inhibition site which is absent from the first three Ig domains.