Liu Guofa, Li Weiquan, Gao Xue, Li Xiaoling, Jürgensen Claudia, Park Hwan-Tae, Shin Nah-Young, Yu Jian, He Ming-Liang, Hanks Steven K, Wu Jane Y, Guan Kun-Liang, Rao Yi
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
J Neurosci. 2007 Jan 24;27(4):957-68. doi: 10.1523/JNEUROSCI.4616-06.2007.
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.
网蛋白是轴突导向信号的一个重要家族。在此,我们报告网蛋白-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)位于Src家族激酶的下游以及小GTP酶Rac1和Cdc42的上游。抑制p130(CAS)信号传导会阻断网蛋白-1的神经突生长促进活性和轴突吸引活性。p130(CAS)RNA干扰抑制网蛋白-1对脊髓中联合轴突的吸引,并导致胚胎中联合轴突投射缺陷。这些结果表明,p130(CAS)是网蛋白信号转导途径中的关键成分,在体内引导联合轴突方面发挥重要作用。