Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, NY 10021, USA.
Biochem Biophys Res Commun. 2011 Sep 16;413(1):92-7. doi: 10.1016/j.bbrc.2011.08.060. Epub 2011 Aug 22.
Upon spinal cord injury, the myelin inhibitors, including the myelin-associated glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp), bind to and signal via a single neuronal receptor/co-receptor complex comprising of Nogo receptor 1(NgR1)/LINGO-1 and p75 or TROY, impeding regeneration of injured axons. We employed a cell-free system to study the binding of NgR1 to its co-receptors and the myelin inhibitor Nogo-A, and show that gangliosides mediate the interaction of NgR1 with LINGO-1. Solid phase binding assays demonstrate that the sialic acid moieties of gangliosides and the stalk of NgR1 are the principal determinants of these molecular interactions. Moreover, the tripartite complex comprising of NgR1, LINGO-1 and ganglioside exhibits stronger binding to Nogo-A (Nogo-54) in the presence of p75, suggesting the gangliosides modulate the myelin inhibitor-receptor signaling.
脊髓损伤后，髓鞘抑制剂，包括髓鞘相关糖蛋白（MAG）、Nogo-A 和少突胶质细胞髓鞘糖蛋白（OMgp），通过由 Nogo 受体 1（NgR1）/LINGO-1 和 p75 或 TROY 组成的单一神经元受体/共受体复合物结合并发出信号，阻碍受损轴突的再生。我们利用无细胞系统研究了 NgR1 与其共受体和髓鞘抑制剂 Nogo-A 的结合，并表明神经节苷脂介导 NgR1 与 LINGO-1 的相互作用。固相结合分析表明，神经节苷脂的唾液酸部分和 NgR1 的柄部是这些分子相互作用的主要决定因素。此外，在 p75 存在的情况下，由 NgR1、LINGO-1 和神经节苷脂组成的三联复合物与 Nogo-A（Nogo-54）表现出更强的结合，表明神经节苷脂调节髓鞘抑制剂-受体信号。
