A central step in organizing the central nervous system development is the growth cone of an axon navigating through guidance cues to reach its specific target. While a great deal of this process has been understood especially in identifying the extracellular guidance cues and their membrane receptors, much less is known about how guidance signals are further relayed to the actin filaments that are central to the mobility of the growth cone. The previous results from our laboratory have shown that Drosophila gene dunc-115 regulates axon projection in the eye and the central nervous system. Furthermore, Dunc-115 has a villin-headpiece (VHD) domain, implying the possibility of binding to actin. To further characterize Dunc-115’s functions, we have identified the isoform Dunc-115L as a possible downstream target in relaying guidance cues further down to the cytoskeleton. Specifically, we have shown that Dunc-115 regulates neural connections in both the eye and the central nervous system in Drosophila and that Dunc-115 contains an actin-binding domain potentially capable of binding to actin filaments. In this report, we show that Dunc-115 binds to actin via its VHD domain directly, suggesting a possible mechanism for how Dunc-115 relays guidance signals.

中文翻译：

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果蝇Dunc-115通过肌动蛋白结合介导轴突投射。

组织中枢神经系统发育的中心步骤是轴突的生长锥，它通过引导提示进行导航以达到其特定目标。尽管在识别细胞外引导线索及其膜受体方面已经了解了很多这样的过程，但对于如何将引导信号进一步中继到对生长锥移动性至关重要的肌动蛋白丝方面却知之甚少。我们实验室的先前结果表明，果蝇基因dunc - 115调节眼睛和中枢神经系统的轴突投射。此外，Dunc-115具有villin-headpiece（VHD）域，这暗示可能与肌动蛋白结合。为了进一步表征Dunc-115的功能，我们已将同工型Dunc-115L确定为可能将下游信号转导至细胞骨架的下游靶标。具体而言，我们已经表明Dunc-115调节果蝇中眼睛和中枢神经系统的神经连接，并且Dunc-115包含可能与肌动蛋白丝结合的肌动蛋白结合域。在此报告中，我们显示了Dunc-115直接通过其VHD域与肌动蛋白结合，为Dunc-115如何中继指导信号提出了可能的机制。