Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth
Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth
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DOI：
10.1016/s0896-6273(02)00770-5
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发表时间：
2002-07-18
期刊：
影响因子：
16.2
通讯作者：
Filbin, MT
中科院分区：
文献类型：
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作者：
Domeniconi, M;Cao, ZU;Filbin, MT
轴突再生的髓鞘抑制剂，如Nogo和MAG，阻断成年CNS损伤后的再生。虽然Nogo（NgR）的GPI连接受体已被确定，MAG的受体是未知的。我们发现MAG通过与NgR相互作用抑制再生。如果神经元GPI连接的蛋白质被切割，MAG的结合和抑制作用就会丧失。MAG与表达NgR的细胞的结合是GPI依赖性的并且是唾液酸非依赖性的。相反，NgR与表达MAG的细胞结合。MAG，而不是结合神经元但不抑制再生的截短MAG，从NgR表达细胞、DRG和小脑神经元沉淀NgR。重要的是，NgR抗体、可溶性NgR或显性阴性NgR各自防止MAG对神经突生长的抑制。此外，MAG和Nogo66竞争结合NgR。这些结果表明髓鞘抑制剂的冗余，并指示CNS损伤的治疗。
Myelin inhibitors of axonal regeneration, like Nogo and MAG, block regrowth after injury to the adult CNS. While a GPI-linked receptor for Nogo (NgR) has been identified, MAG's receptor is unknown. We show that MAG inhibits regeneration by interaction with NgR. Binding of and inhibition by MAG are lost if neuronal GPI-linked proteins are cleaved. Binding of MAG to NgR-expressing cells is GPI dependent and sialic acid independent. Conversely, NgR binds to MAG-expressing cells. MAG, but not a truncated MAG that binds neurons but does not inhibit regeneration, precipitates NgR from NgR-expressing cells, DRG, and cerebellar neurons, Importantly, NgR antibody, soluble NgR, or dominant-negative NgR each prevent inhibition of neurite outgrowth by MAG. Also, MAG and Nogo66 compete for binding to NgR. These results suggest redundancy in myelin inhibitors and indicate therapies for CNS injuries.