BACKGROUND Abelson tyrosine kinase (Abl) plays a key role in axon guidance in linking guidance receptors to actin dynamics. The long C-terminal domain (CTD) of Drosophila Abl is important for this role, and previous work identified the 'first quarter' (1Q) of the CTD as essential. Here, we link the physical interactions of 1Q binding partners to Abl's function in axon guidance. METHODS Protein binding partners of 1Q were identified by GST pulldown and mass spectrometry, and validated using axon guidance assays in the embryonic nerve cord and motoneurons. The role of 1Q was assessed genetically, utilizing a battery of Abl transgenes in combination with mutation or overexpression of the genes of pulled down proteins, and their partners in actin dynamics. The set of Abl transgenes had the following regions deleted: all of 1Q, each half of 1Q ('eighths', 1E and 2E) or a PxxP motif in 2E, which may bind SH3 domains. RESULTS GST pulldown identified Hem and Sra-1 as binding partners of 1Q, and our genetic analyses show that both proteins function with Abl in axon guidance, with Sra-1 likely interacting with 1Q. As Hem and Sra-1 are part of the actin-polymerizing WAVE regulatory complex (WRC), we extended our analyses to Abi and Trio, which interact with Abl and WRC members. Overall, the 1Q region (and especially 2E and its PxxP motif) are important for Abl's ability to work with WRC in axon guidance. These areas are also important for Abl's ability to function with the actin regulator Enabled. In comparison, 1E contributes to Abl function with the WRC at the midline, but less so with Enabled. CONCLUSIONS The 1Q region, and especially the 2E region with its PxxP motif, links Abl with the WRC, its regulators Trio and Abi, and the actin regulator Ena. Removing 1E has specific effects suggesting it may help modulate Abl's interaction with the WRC or Ena. Thus, the 1Q region of Abl plays a key role in regulating actin dynamics during axon guidance.

中文翻译：

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Abelson 的 C 端域的第一季度调节 WAVE 调节复合体并在轴突引导中启用。

背景 Abelson 酪氨酸激酶 (Abl) 在将导向受体与肌动蛋白动力学联系起来的轴突导向中起关键作用。果蝇 Abl 的长 C 端域 (CTD) 对此作用很重要，之前的工作确定 CTD 的“第一季度”(1Q) 是必不可少的。在这里，我们将 1Q 结合伙伴的物理相互作用与 Abl 在轴突引导中的功能联系起来。方法 通过 GST pulldown 和质谱法鉴定 1Q 的蛋白质结合配偶体，并在胚胎神经索和运动神经元中使用轴突引导测定法进行验证。1Q 的作用是通过遗传评估的，利用一组 Abl 转基因结合下拉蛋白基因的突变或过度表达，以及它们在肌动蛋白动力学中的伙伴。Abl 转基因组删除了以下区域：所有 1Q、1Q 的每一半（“八分之一”、1E 和 2E）或 2E 中的 PxxP 基序，可以结合 SH3 域。结果 GST pulldown 将 Hem 和 Sra-1 鉴定为 1Q 的结合伙伴，我们的遗传分析表明，这两种蛋白质在轴突引导中与 Abl 一起发挥作用，Sra-1 可能与 1Q 相互作用。由于 Hem 和 Sra-1 是肌动蛋白聚合 WAVE 调节复合体 (WRC) 的一部分，我们将分析扩展到 Abi 和 Trio，它们与 Abl 和 WRC 成员相互作用。总体而言，1Q 区域（尤其是 2E 及其 PxxP 基序）对于 Abl 在轴突引导中与 WRC 合作的能力很重要。这些区域对于 Abl 在肌动蛋白调节器启用的情况下发挥作用的能力也很重要。相比之下，WRC 位于中线时 1E 对 Abl 功能有贡献，但在启用时则较少。结论 第一季度地区，尤其是带有 PxxP 基序的 2E 区域，将 Abl 与 WRC、其调节因子 Trio 和 Abi 以及肌动蛋白调节因子 Ena 联系起来。去除 1E 具有特定效果，表明它可能有助于调节 Abl 与 WRC 或 Ena 的相互作用。因此，Abl 的 1Q 区域在轴突引导过程中调节肌动蛋白动力学中起着关键作用。