Soluble myelin-associated glycoprotein (MAG) found in vivo inhibits axonal regeneration
Soluble myelin-associated glycoprotein (MAG) found in vivo inhibits axonal regeneration
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DOI：
10.1006/mcne.1997.0633
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发表时间：
1997-01-01
影响因子：
3.5
通讯作者：
Filbin, MT
中科院分区：
文献类型：
--
作者：
Tang, S;Woodhall, RW;Filbin, MT
髓鞘相关糖蛋白(MAG)是一种强有力的轴突再生抑制物，当用作生长的底物时。然而，为了明确地将MAG定性为抑制性而不是非允许性，MAG在溶液中也必须抑制轴突再生。在这里，我们显示了从髓鞘中大量释放并在体内发现的可溶性dMAG(仅细胞外域)和嵌合的MAG-Fc，可以有效地抑制轴突再生。对于dMAG和MAG-Fc，抑制作用均呈剂量依赖性。如果髓鞘条件培养液中的dMAG免疫耗尽，或者MAG-Fc中含有MAG抗体，则抑制作用完全被中和。结合MAG诱导生长锥塌陷的能力，这些结果表明MAG是一种抑制分子，而不仅仅是不允许的。结果还表明，MAG与特定的受体结合，并启动信号转导级联反应，从而产生抑制作用。重要的是，这些结果表明，体内检测到的可溶性dMAG可能导致哺乳动物中枢神经系统损伤后缺乏再生。
Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal regeneration when used as a substrate for growth. However, to be characterized definitively as inhibitory rather than nonpermissive, MAG must also inhibit axonal regeneration when presented in solution. Here, we show that soluble dMAG (extracellular domain only), released in abundance from myelin and found in vivo and chimeric MAG-Fc, can potently inhibit axonal regeneration. For both dMAG and MAG-Fc, inhibition is dose-dependent. If myelin-conditioned medium is immunodepleted of dMAG, or if a MAG antibody is included with MAG-Fc, inhibition is completely neutralized. Together with MAG's ability to induce growth cone collapse, these results demonstrate that MAG is an inhibitory molecule and not merely nonpermissive. The results also suggest that MAG binds to a specific receptor and initiates a signal transduction cascade to effect inhibition. Importantly, these results indicate that soluble dMAG detected in vivo could contribute to the lack of regeneration in the mammalian CNS after injury.