Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline
Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline
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DOI：
10.1016/s0896-6273(03)00591-9
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发表时间：
2003-09-25
期刊：
影响因子：
16.2
通讯作者：
Bashaw, GJ
中科院分区：
文献类型：
--
作者：
Fan, XP;Labrador, JP;Bashaw, GJ
Drosophila Roundabout （Robo）是一个保守的排斥轴突引导受体家族的创始成员，该家族对分泌的Slit蛋白作出反应。在这里，我们提出证据表明SH3-SH2接头蛋白Dreadlocks （Dock）、p21激活的丝氨酸-苏氨酸激酶（Pak）和Rac1/Rac2/Mtl小GTPases可以在Robo排斥过程中发挥作用。功能丧失和基因相互作用实验表明，限制Dock、Pak或Rac的功能会部分破坏Robo斥力。此外，Dock可以直接结合到Robo的细胞质结构域，并且通过Slit刺激可以增强Dock与Robo的关联。此外，狭缝刺激可以将Dock和Pak复合物招募到Robo受体，并触发Rac1活性的增加。这些结果提供了Robo受体和一个重要的细胞骨架调节蛋白复合物之间的直接物理联系，并表明Rac可以在吸引和排斥轴突引导中发挥作用。
Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Here we present evidence that the SH3-SH2 adaptor protein Dreadlocks (Dock), the p21-activated serine-threonine kinase (Pak), and the Rac1/Rac2/Mtl small GTPases can function during Robo repulsion. Loss-of-function and genetic interaction experiments suggest that limiting the function of Dock, Pak, or Rac partially disrupts Robo repulsion. In addition, Dock can directly bind to Robo's cytoplasmic domain, and the association of Dock and Robo is enhanced by stimulation with Slit. Furthermore, Slit stimulation can recruit a complex of Dock and Pak to the Robo receptor and trigger an increase in Rac1 activity. These results provide a direct physical link between the Robo receptor and an important cytoskeletal regulatory protein complex and suggest that Rac can function in both attractive and repulsive axon guidance.