During the development of the nervous system, axons extend through complex environments. Growth cones at the axon tip allow axons to find and innervate their appropriate targets and form functional synapses. Axon pathfinding requires axons to respond to guidance signals and these cues need to be detected by specialized receptors followed by intracellular signal integration and translation. Several downstream signaling pathways have been identified for axon guidance receptors and it has become evident that these pathways are often initiated from intracellular vesicles called endosomes. Endosomes allow receptors to traffic intracellularly, re-locating receptors from one cellular region to another. The localization of axon guidance receptors to endosomal compartments is crucial for their function, signaling output and expression levels. For example, active receptors within endosomes can recruit downstream proteins to the endosomal membrane and facilitate signaling. Also, endosomal trafficking can re-locate receptors back to the plasma membrane to allow re-activation or mediate downregulation of receptor signaling via degradation. Accumulating evidence suggests that axon guidance receptors do not follow a pre-set default trafficking route but may change their localization within endosomes. This re-routing appears to be spatially and temporally regulated, either by expression of adaptor proteins or co-receptors. These findings shed light on how signaling in axon guidance is regulated and diversified - a mechanism which explains how a limited set of guidance cues can help to establish billions of neuronal connections. In this review, we summarize and discuss our current knowledge of axon guidance receptor trafficking and provide directions for future research.

在神经系统的发育过程中，轴突在复杂的环境中延伸。轴突尖端的生长锥允许轴突找到并支配其适当的目标并形成功能性突触。轴突寻路需要轴突对引导信号做出反应，这些线索需要由专门的受体检测，然后进行细胞内信号整合和翻译。已经确定了轴突导向受体的几个下游信号通路，并且很明显这些通路通常是从称为内体的细胞内囊泡开始的。内体允许受体在细胞内运输，将受体从一个细胞区域重新定位到另一个细胞区域。轴突导向受体定位于内体区室对其功能、信号输出和表达水平至关重要。例如，内体内的活性受体可以将下游蛋白质募集到内体膜并促进信号传导。此外，内体运输可以将受体重新定位回质膜，以允许重新激活或通过降解介导受体信号的下调。越来越多的证据表明，轴突导向受体不遵循预设的默认运输路线，但可能会改变它们在内体内的定位。这种重新路由似乎在空间和时间上受到调节，无论是通过接头蛋白的表达还是辅助受体的表达。这些发现阐明了轴突引导中的信号是如何被调节和多样化的——这一机制解释了一组有限的引导线索如何帮助建立数十亿个神经元连接。在这次审查中，