Nuclear migration is critical for the proper positioning of neurons in the developing brain. It is known that bidirectional microtubule motors are required for nuclear transport, yet the mechanism of the coordination of opposing motors is still under debate. Using mouse cerebellar granule cells, we demonstrate that Nesprin-2 serves as a nucleus-motor adaptor, coordinating the interplay of kinesin-1 and dynein. Nesprin-2 recruits dynein-dynactin-BicD2 independently of the nearby kinesin-binding LEWD motif. Both motor binding sites are required to rescue nuclear migration defects caused by the loss of function of Nesprin-2. In an intracellular cargo transport assay, the Nesprin-2 fragment encompassing the motor binding sites generates persistent movements toward both microtubule minus and plus ends. Nesprin-2 drives bidirectional cargo movements over a prolonged period along perinuclear microtubules, which advance during the migration of neurons. We propose that Nesprin-2 keeps the nucleus mobile by coordinating opposing motors, enabling continuous nuclear transport along advancing microtubules in migrating cells.

中文翻译：

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Nesprin-2 在神经元核迁移过程中协调相反的微管运动。


核迁移对于发育中的大脑中神经元的正确定位至关重要。众所周知，核运输需要双向微管马达，但相反马达的协调机制仍存在争议。使用小鼠小脑颗粒细胞，我们证明 Nesprin-2 作为核运动适配器，协调驱动蛋白-1 和动力蛋白的相互作用。 Nesprin-2 独立于附近的驱动蛋白结合 LEWD 基序募集动力蛋白-dynactin-BicD2。需要两个运动结合位点来挽救 Nesprin-2 功能丧失引起的核迁移缺陷。在细胞内货物运输测定中，包含运动结合位点的 Nesprin-2 片段产生朝向微管负端和正端的持续运动。 Nesprin-2 沿着核周微管长期驱动双向货物运动，该微管在神经元迁移过程中前进。我们提出 Nesprin-2 通过协调相反的马达来保持细胞核的移动，从而使细胞核能够沿着迁移细胞中前进的微管进行连续运输。