Centre de Recherche en Biologie Cellulaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique, Montpellier, France.
Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, Netherlands.
J Cell Biol. 2020 Sep 7;219(9). doi: 10.1083/jcb.201905199.
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.
微管（MT）正极追踪蛋白（+TIPs）是在轴突导向过程中生长锥（GC）中 MT 和肌动蛋白细胞骨架之间协调的核心参与者。+TIP 导航器-1（NAV1）在发育中的神经系统中表达，但它的神经元功能仍未得到充分阐明。在这里，我们报告说 NAV1 以 EB1 依赖性的方式控制皮质神经元的轴突 GC 的动力学和运动性，并且对于朝向 netrin-1 梯度的轴突转向是必需的。NAV1 在 GC 的富含 F-肌动蛋白的区域中积累，并在体外与肌动蛋白丝结合。NAV1 也可以在体外独立于 EB1 与非聚合 MT 正极结合，并将非聚合 MT 正极交联到轴突 GC 中的肌动蛋白丝上，从而防止富含 F-肌动蛋白的区域中的 MT 解聚。总之，我们的发现指出 NAV1 是促进 MT 在 GC 周围持续存在并调节 GC 转向的肌动蛋白-MT 串扰中的关键参与者。此外，我们提供的数据将 NAV1 在体内皮质投射神经元的放射状迁移中分配了一个重要角色。
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