LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex
LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex
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DOI：
10.1038/nn1188
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发表时间：
2004-03-01
影响因子：
25
通讯作者：
Pepinsky, RB
中科院分区：
文献类型：
--
作者：
Mi, S;Lee, X;Pepinsky, RB
髓鞘中的抑制剂阻止成年CNS中的轴突再生。这些抑制剂似乎通过与包含配体结合亚基（Nogo-66受体NgR 1）和信号转导亚基（神经营养因子受体p75）的受体复合物结合来调节RhoA活性。然而，在重建的非神经元系统中，NgR 1和p75一起不能激活RhoA，这表明可能存在受体的其他成分。在这里，我们描述LINGO-1，神经系统特异性跨膜蛋白结合NgR 1和p75，这是一个额外的功能组件的NgR 1/p75信号复合物。在非神经元细胞中，人NgR 1，p75和LINGO-1的共表达赋予了对少突胶质细胞髓鞘糖蛋白的反应性，如通过RhoA活化所测量的。显性阴性人LINGO-1构建体在转染的原代神经元培养物中减弱髓鞘抑制。使用外源添加的人LINGO-1-Fc融合蛋白模拟对神经元的这种作用。总之，这些观察结果表明LINGO-1在CNS生物学中具有重要作用。
Axon regeneration in the adult CNS is prevented by inhibitors in myelin. These inhibitors seem to modulate RhoA activity by binding to a receptor complex comprising a ligand-binding subunit (the Nogo-66 receptor NgR1) and a signal transducing subunit (the neurotrophin receptor p75). However, in reconstituted non-neuronal systems, NgR1 and p75 together are unable to activate RhoA, suggesting that additional components of the receptor may exist. Here we describe LINGO-1, a nervous system-specific transmembrane protein that binds NgR1 and p75 and that is an additional functional component of the NgR1/p75 signaling complex. In non-neuronal cells, coexpression of human NgR1, p75 and LINGO-1 conferred responsiveness to oligodendrocyte myelin glycoprotein, as measured by RhoA activation. A dominant-negative human LINGO-1 construct attenuated myelin inhibition in transfected primary neuronal cultures. This effect on neurons was mimicked using an exogenously added human LINGO-1-Fc fusion protein. Together these observations suggest that LINGO-1 has an important role in CNS biology.