p130CAS is required for netrin signaling and commissural axon guidance
p130CAS is required for netrin signaling and commissural axon guidance
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DOI：
10.1523/jneurosci.4616-06.2007
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发表时间：
2007-01-24
影响因子：
5.3
通讯作者：
Rao, Yi
中科院分区：
文献类型：
--
作者：
Liu, Guofa;Li, Weiquan;Rao, Yi
Netrins 是轴突引导线索的重要家族。在这里，我们报告 netrin-1 诱导 p130(CAS)（Crk 相关底物）的酪氨酸磷酸化。我们的生化研究表明 p130(CAS) 是 Src 家族激酶的下游以及小 GTPase Rac1 和 Cdc42 的上游。抑制 p130(CAS) 信号传导会阻断 netrin-1 的神经突生长促进活性和轴突吸引活性。 p130(CAS) RNA 干扰抑制 netrin-1 对脊髓中连合轴突的吸引，并导致胚胎中连合轴突投射缺陷。这些结果表明p130(CAS)是netrin信号转导途径的关键组成部分，在体内引导连合轴突中发挥重要作用。
Netrins are an important family of axon guidance cues. Here, we report that netrin- 1 induces tyrosine phosphorylation of p130(CAS) (Crk-associated substrate). Our biochemical studies indicate that p130(CAS) is downstream of the Src family kinases and upstream of the small GTPase Rac1 and Cdc42. Inhibition of p130(CAS) signaling blocks both the neurite outgrowth-promoting activity and the axon attraction activity of netrin-1. p130(CAS) RNA interference inhibits the attraction of commissural axons in the spinal cord by netrin-1 and causes defects in commissural axon projection in the embryo. These results demonstrate that p130(CAS) is a key component in the netrin signal transduction pathway and plays an important role in guiding commissural axons in vivo.