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肌球蛋白结合蛋白 Anillin 通过连接 RhoG 到肌动蛋白细胞骨架来调节神经元迁移和轴突生长。

Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton.

机构信息

Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.

出版信息

Curr Biol. 2015 May 4;25(9):1135-45. doi: 10.1016/j.cub.2015.02.072. Epub 2015 Apr 2.

Abstract

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 the C. elegans Q 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.

摘要

神经元迁移和轴突生长是神经发育过程中的重要事件,但目前尚不清楚指导线索如何通过受体转导到肌动蛋白细胞骨架,而肌动蛋白细胞骨架为这些过程提供动力。我们报告说,有丝分裂支架蛋白 Anillin 在 C. elegans Q 神经母细胞的细胞迁移和轴突生长过程中重新分布到前端。为了绕过细胞分裂过程中对 Anillin 的需求,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 通过在前沿稳定 F-actin 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 的肌动蛋白结合域通过拮抗肌动蛋白丝切断活性的 Cofilin 足以稳定 F-actin。我们进一步揭示出活性形式的 RhoG/MIG-2 直接与 Anillin 结合并将其募集到前沿。我们的结果揭示了一种新的途径,其中 Anillin 在神经元迁移和轴突生长过程中,将 RhoG 信号转导到肌动蛋白细胞骨架。

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