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Axon-Axon Interactions Regulate Topographic Optic Tract Sorting via CYFIP2-Dependent WAVE Complex Function.
Neuron ( IF 14.7 ) Pub Date : 2018-Mar-07 , DOI: 10.1016/j.neuron.2018.01.027
Jean-Michel Cioni 1 , Hovy Ho-Wai Wong 1 , Dario Bressan 2 , Lay Kodama 1 , William A Harris 1 , Christine E Holt 1
Affiliation  

The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that cytoplasmic FMR1-interacting proteins (CYFIPs) fulfill non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons. CYFIP2 associates with transporting ribonucleoprotein particles in axons and regulates translation. Axon-axon contact stimulates CYFIP2 to move into growth cones where it joins the actin nucleating WAVE regulatory complex (WRC) in the periphery and regulates actin remodeling and filopodial dynamics. CYFIP2's function in axon sorting is mediated by its binding to the WRC but not its translational regulation. Together, these findings uncover CYFIP2 as a key regulatory link between axon-axon interactions, filopodial dynamics, and optic tract sorting.

中文翻译:

轴突-轴突相互作用通过 CYFIP2 相关波复合函数调节地形视束分类。

视网膜神经节细胞 (RGC) 的轴突在到达视顶盖之前进行了地形分类。这种预目标排序,典型的贯穿大脑的轴突束,人们知之甚少。在这里,我们显示细胞质 FMR1 相互作用蛋白 (CYFIP) 在 RGC 中实现非冗余功能,CYFIP1 介导轴突生长,CYFIP2 专门参与轴突分选。我们发现 CYFIP2 介导背侧和腹侧轴突之间的同型和异型接触触发的束颤和排斥反应。CYFIP2 与轴突中的核糖核蛋白颗粒转运相关并调节翻译。轴突-轴突接触刺激 CYFIP2 移动到生长锥中,在那里它加入外围的肌动蛋白成核 WAVE 调节复合物 (WRC) 并调节肌动蛋白重塑和丝状足动力学。CYFIP2' 轴突分选中的 s 功能是由其与 WRC 的结合介导的,而不是其翻译调节。总之,这些发现揭示了 CYFIP2 作为轴突-轴突相互作用、丝足动力学和视束分类之间的关键调节联系。
更新日期:2018-03-08
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