Tang S, Woodhall R W, Shen Y J, deBellard M E, Saffell J L, Doherty P, Walsh F S, Filbin M T
Department of Biological Sciences, Hunter College of the City University of New York 10021, USA.
Mol Cell Neurosci. 1997;9(5-6):333-46. doi: 10.1006/mcne.1997.0633.
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.
髓磷脂相关糖蛋白（MAG）用作生长底物时是轴突再生的强效抑制剂。然而，要明确其为抑制性而非非许可性，MAG在溶液中存在时也必须抑制轴突再生。在此，我们表明，从髓磷脂中大量释放、在体内发现的可溶性dMAG（仅细胞外结构域）以及嵌合MAG-Fc能够有效抑制轴突再生。对于dMAG和MAG-Fc而言，抑制作用均呈剂量依赖性。如果对髓磷脂条件培养基进行免疫去除dMAG处理，或者在MAG-Fc中加入MAG抗体，抑制作用会完全被中和。结合MAG诱导生长锥塌陷的能力，这些结果表明MAG是一种抑制性分子，而不仅仅是非许可性分子。这些结果还表明，MAG与特定受体结合并启动信号转导级联反应以实现抑制作用。重要的是，这些结果表明，在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再生能力的缺失。
