Calsyntenin 1-mediated trafficking of axon guidance receptors regulates the switch in axonal responsiveness at a choice point
Calsyntenin 1-mediated trafficking of axon guidance receptors regulates the switch in axonal responsiveness at a choice point
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DOI：
10.1242/dev.127449
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发表时间：
2016-03-15
期刊：
影响因子：
4.6
通讯作者：
Stoeckli, Esther T.
中科院分区：
文献类型：
--
作者：
Alther, Tobias A.;Domanitskaya, Elena;Stoeckli, Esther T.
选择点的轴突引导取决于生长锥表面引导受体的精确调节。到达中间目标或选择点后，轴突需要从吸引切换到排斥才能继续前进。穿过底板中脊髓腹侧中线的背连合（dI1）轴突代表了分析轴突行为转换背后的分子机制的便捷模型。我们在小鸡中发现了 Calsyntenin 1 在调节 dI1 轴突选择点的引导受体的囊泡运输中的作用。与 RabGDI 合作，Calsyntenin 1 以精确调控的方式将含有 Robo1 的 Rab11 阳性囊泡运送到生长锥表面。相比之下，Calsyntenin 1 介导的卷曲 3（Wnt 通路中的引导受体）的运输不依赖于 RabGDI。因此，引导受体的严格调节插入是通过特定的运输来实现的，这是中线穿过和随后转向纵轴所必需的。
Axon guidance at choice points depends on the precise regulation of guidance receptors on the growth cone surface. Upon arrival at the intermediate target or choice point, a switch from attraction to repulsion is required for the axon to move on. Dorsal commissural (dI1) axons crossing the ventral midline of the spinal cord in the floor plate represent a convenient model for the analysis of the molecular mechanism underlying the switch in axonal behavior. We identified in chick a role for calsyntenin 1 in the regulation of vesicular trafficking of guidance receptors in dI1 axons at choice points. In cooperation with RabGDI, calsyntenin 1 shuttles Rab11-positive vesicles containing Robo1 to the growth cone surface in a precisely regulated manner. By contrast, calsyntenin 1-mediated trafficking of frizzled 3, a guidance receptor in the Wnt pathway, is independent of RabGDI. Thus, tightly regulated insertion of guidance receptors, which is required for midline crossing and the subsequent turn into the longitudinal axis, is achieved by specific trafficking.