IDENTIFICATION OF MYELIN-ASSOCIATED GLYCOPROTEIN AS A MAJOR MYELIN-DERIVED INHIBITOR OF NEURITE GROWTH

IDENTIFICATION OF MYELIN-ASSOCIATED GLYCOPROTEIN AS A MAJOR MYELIN-DERIVED INHIBITOR OF NEURITE GROWTH
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DOI:
10.1016/0896-6273(94)90247-x
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发表时间:
1994-10-01
期刊:
影响因子:
16.2
通讯作者:
BRAUN, PE
BRAUN, PE
中科院分区:
医学1区
文献类型:
--
作者:
MCKERRACHER, L;DAVID, S;BRAUN, PE

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中枢神经系统髓鞘中存在接触性轴突生长抑制活性,但其抑制蛋白的特性尚未完全确定。我们在这里报道,通过DEAE层析分离溶解的CNS髓鞘蛋白,至少可以分离出两个抑制活性峰。抑制活性的主峰对应于髓鞘相关糖蛋白(MAC)的洗脱图谱。这些抑制组分中MAG的免疫耗竭消除了对轴突生长的抑制,而重组MAC(胞外结构域)是一种有效的轴突生长抑制物。免疫去除中枢神经系统髓鞘总提取液中的MAG后,轴突生长恢复到对照水平的63%。这些结果表明,MAC是中枢神经系统髓鞘中一个重要的,而且可能是主要的抑制因子;这对受损的哺乳动物中枢神经系统的轴突再生具有广泛的意义。
Contact-dependent axon growth inhibitory activity is present in CNS myelin, but the inhibitory proteins have not been fully characterized. We report here that at least two peaks of inhibitory activity can be separated by fractionating solubilized CNS myelin proteins by DEAE chromatography. A major peak of inhibitory activity corresponded to the elution profile of myelin-associated glycoprotein (MAC). Immunodepletion of MAG from these inhibitory fractions removed neurite growth inhibition, whereas recombinant MAC (ectodomain) was a potent inhibitor of neurite outgrowth. Immunodepletion of MAG from total extracts of CNS myelin restored neurite growth up to 63% of control levels. These results establish that MAC is a significant, and possibly the major, inhibitor in CNS myelin; this has broad implications for axonal regeneration in the injured mammalian CNS.