Domeniconi Marco, Cao Zixuan, Spencer Timothy, Sivasankaran Rajeev, Wang Kevin, Nikulina Elena, Kimura Noriko, Cai Hong, Deng Kangwen, Gao Ying, He Zhigang, Filbin Marie
The Department of Biological Sciences, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10021, USA.
Neuron. 2002 Jul 18;35(2):283-90. doi: 10.1016/s0896-6273(02)00770-5.
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.
轴突再生的髓磷脂抑制剂，如Nogo和MAG，会在成年中枢神经系统损伤后阻断其再生。虽然已鉴定出Nogo的糖基磷脂酰肌醇（GPI）连接受体（NgR），但MAG的受体尚不清楚。我们发现MAG通过与NgR相互作用来抑制再生。如果神经元的GPI连接蛋白被切割，MAG的结合及抑制作用就会丧失。MAG与表达NgR的细胞的结合是GPI依赖性的，且不依赖于唾液酸。相反，NgR能与表达MAG的细胞结合。MAG（而非与神经元结合但不抑制再生的截短型MAG）能从表达NgR的细胞、背根神经节（DRG）和小脑神经元中沉淀出NgR。重要的是，NgR抗体、可溶性NgR或显性负性NgR均可阻止MAG对神经突生长的抑制作用。此外，MAG和Nogo66竞争与NgR的结合。这些结果表明髓磷脂抑制剂存在冗余，并为中枢神经系统损伤指明了治疗方法。
