Wong Scott T, Henley John R, Kanning Kevin C, Huang Kuo-hua, Bothwell Mark, Poo Mu-ming
Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Nat Neurosci. 2002 Dec;5(12):1302-8. doi: 10.1038/nn975.
Myelin-associated glycoprotein (MAG), an inhibitor of axon regeneration, binds with high affinity to the Nogo-66 receptor (NgR). Here we report that the p75 neurotrophin receptor (p75(NTR)) is a co-receptor of NgR for MAG signaling. In cultured human embryonic kidney (HEK) cells expressing NgR, p75(NTR) was required for MAG-induced intracellular Ca2+ elevation. Co-immunoprecipitation showed an association of NgR with p75(NTR) that can be disrupted by an antibody against p75(NTR) (NGFR5), and extensive coexpression was observed in the developing rat nervous system. Furthermore, NGFR5 abolished MAG-induced repulsive turning of Xenopus axonal growth cones and Ca2+ elevation, both in neurons and in NgR/p75(NTR)-expressing HEK cells. Thus we conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration.
髓磷脂相关糖蛋白（MAG）是一种轴突再生抑制剂，它与Nogo-66受体（NgR）具有高亲和力结合。在此我们报告，p75神经营养因子受体（p75(NTR)）是NgR介导MAG信号传导的共受体。在表达NgR的培养人胚肾（HEK）细胞中，MAG诱导的细胞内Ca2+升高需要p75(NTR)。免疫共沉淀显示NgR与p75(NTR)存在关联，这种关联可被抗p75(NTR)抗体（NGFR5）破坏，并且在发育中的大鼠神经系统中观察到广泛的共表达。此外，在神经元以及表达NgR/p75(NTR)的HEK细胞中，NGFR5消除了MAG诱导的非洲爪蟾轴突生长锥的排斥性转向和Ca2+升高。因此我们得出结论，p75(NTR)是NgR介导MAG信号传导的共受体，也是促进神经再生的潜在治疗靶点。
