Neogenin mediates the action of repulsive guidance molecule
Neogenin mediates the action of repulsive guidance molecule
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DOI：
10.1038/ncb1156
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发表时间：
2004-08-01
影响因子：
21.3
通讯作者：
Strittmatter, SM
中科院分区：
文献类型：
--
作者：
Rajagopalan, S;Deitinghoff, L;Strittmatter, SM
排斥性引导分子(RGM)是最近发现的一种与轴突引导和神经管关闭有关的蛋白质(1，2)。通过生长颞叶而不是鼻侧的视网膜神经节细胞轴突来避免小鸡顶盖后部的RGM被认为有助于视觉地图的形成。与肾上腺素、信号素、Netrins和狭缝(3，4)相反，尚未定义RGM作用的受体机制。在这里，表达克隆策略确定新生素是RGM的结合部位，具有亚纳摩尔亲和力。与RGM的选择性轴突反应一致，新生素在鸡视网膜上呈梯度表达。新生素是已知的几种Netrin结合蛋白之一(5)，但只有新生素与RGM相互作用。抗新生素抗体和可溶性新生素胞外区阻断了颞侧视网膜轴突对RGM的回避。背根神经节轴突对RGM无反应，但通过新生素的表达而转化为反应状态。因此，新生素作为RGM受体发挥作用。
Repulsive guidance molecule (RGM) is a recently identified protein implicated in both axonal guidance and neural tube closure(1,2). The avoidance of chick RGM in the posterior optic tectum by growing temporal, but not nasal, retinal ganglion cell axons is thought to contribute to visual map formation. In contrast to ephrins, semaphorins, netrins and slits(3,4), no receptor mechanism for RGM action has been defined. Here, an expression cloning strategy identified neogenin as a binding site for RGM, with a sub-nanomolar affinity. Consistent with selective axonal responsiveness to RGM, neogenin is expressed in a gradient across the chick retina. Neogenin is known to be one of several netrin-binding proteins(5) but only neogenin interacts with RGM. The avoidance of RGM by temporal retinal axons is blocked by the anti-neogenin antibody and the soluble neogenin ectodomain. Dorsal root ganglion axons are unresponsive to RGM but are converted to a responsive state by neogenin expression. Thus, neogenin functions as an RGM receptor.