Microtubule (MT) plus-end tracking proteins (+TIPs) are central players in the coordination between the MT and actin cytoskeletons in growth cones (GCs) during axon guidance. The +TIP Navigator-1 (NAV1) is expressed in the developing nervous system, yet its neuronal functions remain poorly elucidated. Here, we report that NAV1 controls the dynamics and motility of the axonal GCs of cortical neurons in an EB1-dependent manner and is required for axon turning toward a gradient of netrin-1. NAV1 accumulates in F-actin–rich domains of GCs and binds actin filaments in vitro. NAV1 can also bind MTs independently of EB1 in vitro and crosslinks nonpolymerizing MT plus ends to actin filaments in axonal GCs, preventing MT depolymerization in F-actin–rich areas. Together, our findings pinpoint NAV1 as a key player in the actin–MT crosstalk that promotes MT persistence at the GC periphery and regulates GC steering. Additionally, we present data assigning to NAV1 an important role in the radial migration of cortical projection neurons in vivo.

中文翻译：

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+TIP Navigator-1 是一种肌动蛋白-微管交联剂，可调节轴突生长锥运动

微管 (MT) 加端跟踪蛋白 (+TIP) 在轴突引导过程中，在生长锥 (GC) 中的 MT 和肌动蛋白细胞骨架之间的协调中发挥着核心作用。+TIP Navigator-1 (NAV1) 在发育中的神经系统中表达，但其神经元功能仍不清楚。在这里，我们报告 NAV1 以 EB1 依赖性方式控制皮质神经元轴突 GC 的动力学和运动性，并且是轴突转向 netrin-1 梯度所必需的。NAV1 在 GC 富含 F-肌动蛋白的结构域中积累，并在体外结合肌动蛋白丝。NAV1 还可以在体外独立于 EB1 结合 MT，并将非聚合 MT 加末端与轴突 GC 中的肌动蛋白丝交联，从而防止富含 F 肌动蛋白的区域中的 MT 解聚。总之，我们的研究结果表明 NAV1 是肌动蛋白-MT 串扰中的关键角色，可促进 MT 在 GC 外围的持久性并调节 GC 转向。此外，我们提供的数据表明 NAV1 在体内皮质投射神经元的径向迁移中发挥着重要作用。