清华大学生科院Cell子刊发现胞质分裂蛋白新分子机制

欧光朔课题组在Current Biology发表论文报道了线虫胞质分裂蛋白Anillin调控神经前体细胞迁移和神经丝生长的机制。

　　

清华大学生命学院欧光朔课题组在近期(2015年5月4日)的Current Biology上发表了题为“Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton”的研究论文，报道线虫(C. elegans)胞质分裂蛋白Anillin在Q神经前体细胞迁移和神经丝生长过程中的重要功能。
 
神经前体细胞迁移和神经丝生长是神经系统发育过程中的关键事件，但是对胞外引导信号如何通过跨膜受体传递到微丝细胞骨架的研究相对较少。为绕过Anillin在胞质分裂过程中的功能，本研究利用体细胞CRISPR－Cas9敲除技术构建了Anillin条件性突变体发现Anillin调控细胞迁移:在细胞前导端(Leading edge)的Anillin 通过拮抗微丝剪切蛋白Cofilin而稳定微丝(F-actin)，促进细胞迁移和神经丝生长锥(Growth cone)的延伸。体外生化实验结果显示，通过拮抗Cofilin的微丝剪切活性，Anillin的微丝结合结构域可以稳定微丝。进一步研究发现小G蛋白RhoG/MIG-2直接结合并招募Anillin到细胞前导端。
 
清华大学生命学院在读博士生田东为本文第一作者，欧光朔研究员为本文的通讯作者。本研究的体外微丝生化实验由黄善金课题组完成,陈柱成课题组在RhoG-Ainllin相互作用方面提供宝贵建议。本项目受到清华-北大生命科学联合中心、科技部、国家自然基金委以及青年****的支持。

RhoG-Anillin-F-actin 调控细胞迁移功能模式图
 
 
原文摘要：

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

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.