Ng Cherry Ee Lin, Tang Bor Luen
NCA Lab, Institute of Molecular and Cell Biology, Singapore, Republic of Singapore.
J Neurosci Res. 2002 Mar 1;67(5):559-65. doi: 10.1002/jnr.10134.
The recently cloned gene Nogo, whose alternative splice products correspond to the antigenic target of the central nervous system (CNS) regeneration enhancing monoclonal antibody IN-1, codes for membrane proteins enriched in brain, particularly in oligodendrocytes. The 66-amino acid extracellular domain of Nogo (Nogo-66) interacts with a high-affinity receptor (NgR), a glycosylphosphatidylinositol (GPI)-linked protein with multiple leucine-rich repeats. The amino terminal cytoplasmic domain of Nogo appears to have a general cellular growth inhibitory effect. Nogo-66, on the other hand, specifically retards neurite outgrowth and induces growth cone collapse, possibly through its interaction with NgR and as yet unidentified transmembrane coreceptors. Recent results also suggest that Nogo expression may induce apoptosis in tumor cells. Together, these proteins provide new molecular handles for the design of therapeutic interventions for CNS injuries and neurodegenerative diseases, as well as possible leads to anticancer strategies.
最近克隆的基因Nogo，其可变剪接产物对应于增强中枢神经系统（CNS）再生的单克隆抗体IN-1的抗原靶点，编码在脑中富集的膜蛋白，特别是在少突胶质细胞中。Nogo的66个氨基酸的细胞外结构域（Nogo-66）与高亲和力受体（NgR）相互作用，NgR是一种具有多个富含亮氨酸重复序列的糖基磷脂酰肌醇（GPI）连接蛋白。Nogo的氨基末端胞质结构域似乎具有一般的细胞生长抑制作用。另一方面，Nogo-66可能通过与NgR和尚未确定的跨膜共受体相互作用，特异性地抑制神经突生长并诱导生长锥塌陷。最近的结果还表明，Nogo表达可能诱导肿瘤细胞凋亡。总之，这些蛋白质为设计针对CNS损伤和神经退行性疾病的治疗干预措施提供了新的分子途径，也可能为抗癌策略提供线索。
