The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons
The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons
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DOI：
10.1038/nn1148
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发表时间：
2003-12-01
影响因子：
25
通讯作者：
Rosenthal, A
中科院分区：
文献类型：
--
作者：
Lin, JC;Ho, WH;Rosenthal, A
Netrin-G1是一种脂质锚定蛋白，在结构上与轴突导向分子的netrin家族相关。Netrin-G1不结合任何已知的netrin受体，其功能尚不清楚。在这里，我们确定了人netrin-G1配体（NGL-1），一种跨膜蛋白，含有富含亮氨酸的重复序列（LRR）和免疫球蛋白（IG）结构域，通过其LRR区域与netrin-G1特异性相互作用。netrin-G1在小鼠丘脑轴突中高度表达，而NGL-1在纹状体和大脑皮质中最丰富，分别是丘脑皮质轴突（TCA）的中间和最终靶点。表面结合的NGL-1刺激，但可溶性NGL-1破坏，胚胎丘脑轴突的生长，体外数据表明，NGL-1的活性可能至少部分介导netrin-G1。我们的研究结果提供的证据表明，netrin-G1作为NGL-1受体的一个重要组成部分，以促进TCA的生长和膜结合netrins可以参与接收轴突信号通路。
Netrin-G1 is a lipid-anchored protein that is structurally related to the netrin family of axon guidance molecules. Netrin-G1 does not bind any of the known netrin receptors and its function is not known. Here we identify human netrin-G1 ligand (NGL-1), a transmembrane protein containing leucine-rich repeat (LRR) and immunoglobulin (Ig) domains that specifically interacts with netrin-G1 through its LRR region. Whereas netrin-G1 is expressed highly in mouse thalamic axons, NGL-1 is most abundant in the striatum and the cerebral cortex the intermediate and final targets, respectively, of thalamocortical axons (TCAs). Surface-bound NGL-1 stimulates, but soluble NGL-1 disrupts, the growth of embryonic thalamic axons, and in vitro data indicate that NGL-1 activity may be mediated at least partially by netrin-G1. Our findings provide evidence that netrin-G1 functions as an important component of the NGL-1 receptor to promote TCA outgrowth and that membrane-bound netrins can participate in receiving axonal signaling pathways.