Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
EMBO J. 2010 Oct 20;29(20):3470-83. doi: 10.1038/emboj.2010.221. Epub 2010 Sep 7.
Wnt signalling is known to promote G1/S progression through the stimulation of gene expression, but whether this signalling regulates mitotic progression is not clear. Here, the function of dishevelled 2 (Dvl2), which transmits the Wnt signal, in mitosis was examined. Dvl2 localized to the spindles and spindle poles during mitosis. When cells were treated with nocodazole, Dvl2 was observed at the kinetochores (KTs). Dvl2 bound to and was phosphorylated at Thr206 by a mitotic kinase, Polo-like kinase 1 (Plk1), and this phosphorylation was required for spindle orientation and stable microtubule (MT)-KT attachment. Dvl2 was also found to be involved in the activation of a spindle assembly checkpoint (SAC) kinase, Mps1, and the recruitment of other SAC components, Bub1 and BubR1, to the KTs. However, the phosphorylation of Dvl2 by Plk1 was dispensable for SAC. Furthermore, Wnt receptors were involved in spindle orientation, but not in MT-KT attachment or SAC. These results suggested that Dvl2 is involved in mitotic progression by regulating the dynamics of MT plus-ends and the SAC in Plk1-dependent and -independent manners.
Wnt 信号被认为通过刺激基因表达来促进 G1/S 期进展,但这种信号是否调节有丝分裂进程尚不清楚。在这里,研究了传递 Wnt 信号的 Dvl2(dishevelled 2)在有丝分裂中的功能。Dvl2 在有丝分裂期间定位于纺锤体和纺锤体极。当用诺考达唑处理细胞时,观察到 Dvl2 位于着丝粒 (KTs)。Dvl2 与有丝分裂激酶 Polo 样激酶 1 (Plk1) 结合,并在 Thr206 处被磷酸化,这种磷酸化对于纺锤体定向和稳定的微管 (MT)-KT 附着是必需的。还发现 Dvl2 参与纺锤体组装检查点 (SAC) 激酶 Mps1 的激活以及其他 SAC 成分 Bub1 和 BubR1 向 KTs 的募集。然而,Plk1 对 Dvl2 的磷酸化对于 SAC 是可有可无的。此外,Wnt 受体参与纺锤体定向,但不参与 MT-KT 附着或 SAC。这些结果表明,Dvl2 通过调节 Plk1 依赖和独立的 MT 末端动力学和 SAC 参与有丝分裂进程。