Myelin-associated glycoprotein interacts with ganglioside GT1b - A mechanism for neurite outgrowth inhibition
Myelin-associated glycoprotein interacts with ganglioside GT1b - A mechanism for neurite outgrowth inhibition
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DOI：
10.1074/jbc.m100345200
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发表时间：
2001-06-08
影响因子：
4.8
通讯作者：
Walsh, FS
中科院分区：
文献类型：
--
作者：
Vinson, M;Strijbos, PJLM;Walsh, FS
髓鞘相关糖蛋白（MAG）表达于髓鞘形成的神经胶质细胞上，并抑制出生后神经元的轴突生长。MAG在其N-末端结构域中具有唾液酸结合位点，并与神经元表面上存在的特异性唾液酸化聚糖和神经节苷脂结合，但这些相互作用在MAG对神经突生长的影响中的意义尚不清楚。在这里，我们提出的证据表明，唾液酸化聚糖的识别是必不可少的抑制神经突起生长的MAG。精氨酸118 MAG是已知的关键接触唾液酸。我表明，该残基的突变降低了MAG抑制活性的效力，但残余活性也是碳水化合物识别的结果。然后我继续研究神经节苷脂GT 1b和GD 1a作为候选MAG受体。我表明，MAG特异性结合两个神经节苷脂，这两个都在MAG反应神经元的表面上表达。此外，细胞表面GT 1b而非GD 1a的抗体交联模拟MAG的作用，因为通过激活Rho激酶抑制神经突生长。这些数据强烈表明，与神经元细胞表面上的GT 1b的相互作用是MAG抑制神经突生长的潜在机制。
Myelin-associated glycoprotein (MAG) is expressed on myelinating glia and inhibits neurite outgrowth from post-natal neurons. MAG has a sialic acid binding site in its N-terminal domain and binds to specific sialylated glycans and gangliosides present on the surface of neurons, but the significance of these interactions in the effect of MAG on neurite outgrowth is unclear. Here we present evidence to suggest that recognition of sialylated glycans is essential for inhibition of neurite outgrowth by MAG. Arginine 118 on MAG is known to make a key contact with sialic acid. me show that mutation of this residue reduces the potency of MAG inhibitory activity hut that residual activity is also a result of carbohydrate recognition. me then go on to investigate gangliosides GT1b and GD1a as candidate MAG receptors. me show that MAG specifically binds both gangliosides and that both are expressed on the surface of MAG-responsive neurons. Furthermore, antibody cross-linking of cell surface GT1b, but not GD1a, mimics the effect of MAG, in that neurite outgrowth is inhibited through activation of Rho kinase, These data strongly suggest that interaction with GT1b on the neuronal cell surface is a potential mechanism for inhibition of neurite outgrowth by MAG.