Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton
Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton
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DOI：
10.1016/j.cub.2015.02.072
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发表时间：
2015-05
期刊：
影响因子：
9.2
通讯作者：
Dong Tian;Min Diao;Yuxiang Jiang;Lingfei Sun;Yan Zhang;Zhucheng Chen;Shanjin Huang;Guangshuo Ou
中科院分区：
文献类型：
--
作者：
Dong Tian;Min Diao;Yuxiang Jiang;Lingfei Sun;Yan Zhang;Zhucheng Chen;Shanjin Huang;Guangshuo Ou
神经元迁移和神经突生长是神经发育中的重要事件，但目前尚不清楚引导信号如何通过受体转导至肌动蛋白细胞骨架，从而为这些过程提供动力。我们报告细胞因子支架蛋白 Anillin 重新分布到 C 的前缘。 elegansQ 神经母细胞在细胞迁移和神经突生长过程中。为了绕过胞质分裂中对 Anillin 的要求，我们使用体细胞 CRISPR-Cas9 技术在 Anillin 中产生条件突变。我们证明 Anillin 通过稳定前沿的 F-肌动蛋白网络来调节细胞迁移和生长锥延伸。我们的生化分析表明，Anillin 的肌动蛋白结合结构域足以通过拮抗 Cofilin 的 F-肌动蛋白切断活性来稳定 F-肌动蛋白。我们进一步发现，RhoG/MIG-2 的活性形式直接与 Anillin 结合并将其招募到前沿。我们的结果揭示了在神经元迁移和神经突生长过程中 Anillin 将 RhoG 信号转导至肌动蛋白细胞骨架的新途径。
Neuronal migration and neurite growth are essential events in neural development, but it remains unclear how guidance cues are transduced through receptors to the actin cytoskeleton, which powers these processes. We report that a cytokinetic scaffold protein, Anillin, is redistributed to the leading edge of theC. elegansQ neuroblast during cell migration and neurite growth. To bypass the requirement for Anillin in cytokinesis, we used the somatic CRISPR-Cas9 technique to generate conditional mutations in Anillin. We demonstrate that Anillin regulates cell migration and growth cone extension by stabilizing the F-actin network at the leading edge. Our biochemical analysis shows that the actin-binding domain of Anillin is sufficient to stabilize F-actin by antagonizing the F-actin severing activity of Cofilin. We further uncover that the active form of RhoG/MIG-2 directly binds to Anillin and recruits it to the leading edge. Our results reveal a novel pathway in which Anillin transduces the RhoG signal to the actin cytoskeleton during neuronal migration and neurite growth.