Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Dev Cell. 2017 Jan 9;40(1):81-94. doi: 10.1016/j.devcel.2016.11.019. Epub 2016 Dec 22.
Mitotic spindle formation and chromosome segregation require timely separation of the two duplicated centrosomes, and this process is initiated in late G2 by centrosome disjunction. Here we report that GAS2L1, a microtubule- and actin-binding protein, associates with the proximal end of mature centrioles and participates in centriole dynamics and centrosome disjunction. GAS2L1 attaches microtubules and actin to centrosomes, and the loss of GAS2L1 inhibits centrosome disjunction in G2 and centrosome splitting induced by depletion of the centrosome linker rootletin. Conversely, GAS2L1 overexpression induces premature centrosome separation, and this activity requires GAS2L1 association with actin, microtubules, and the microtubule end-binding proteins. The centrosome-splitting effect of GAS2L1 is counterbalanced by rootletin, reflecting the opposing actions of GAS2L1 and the centrosome linker. Our work reveals a GAS2L1-mediated centriole-tethering mechanism of microtubules and actin, which provide the forces required for centrosome dynamics and separation.
有丝分裂纺锤体的形成和染色体分离需要两个复制的中心体及时分离，这个过程在 G2 晚期通过中心体分离启动。在这里，我们报告说，GAS2L1 是一种微管和肌动蛋白结合蛋白，与成熟中心粒的近端结合，并参与中心粒动力学和中心体分离。GAS2L1 将微管和肌动蛋白附着到中心体上，并且 GAS2L1 的缺失抑制 G2 中的中心体分离和中心体连接蛋白根蛋白耗尽诱导的中心体分裂。相反，GAS2L1 的过表达诱导中心体过早分离，这种活性需要 GAS2L1 与肌动蛋白、微管和微管末端结合蛋白的结合。GAS2L1 的中心体分裂效应被根蛋白抵消，反映了 GAS2L1 和中心体连接蛋白的拮抗作用。我们的工作揭示了 GAS2L1 介导的微管和肌动蛋白中心粒束缚机制，该机制提供了中心体动力学和分离所需的力。
