Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment.
Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment.
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DOI：
10.1016/j.devcel.2011.01.008
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发表时间：
2011-03-15
影响因子：
11.8
通讯作者：
Mao Y
中科院分区：
文献类型：
--
作者：
Cheng L;Zhang J;Ahmad S;Rozier L;Yu H;Deng H;Mao Y
姐妹动粒与纺锤体的正确双极连接是有丝分裂中染色体精确分离的关键。在这里，我们显示了一个重要的作用，在实现中期染色体排列的mDia 3。该功能独立于mDia 3肌动蛋白成核活性，但可归因于mDia 3的EB 1结合。此外，mDia 3的微管结合FH 2结构域在体外被Aurora B激酶磷酸化，并且表达不可磷酸化的mDia 3突变体的细胞不能将染色体定位在中期板。经Aurora B磷酸化的纯化重组mDia 3在体外结合微管和稳定微管以抵抗冷诱导的解体的能力降低。表达拟磷酸mDia 3突变体的细胞不形成稳定的动粒微管纤维;尽管它们能够将染色体国会到中期板。这些发现揭示了mDia 3及其通过Aurora B磷酸化的调节在实现适当稳定的动粒微管附着中的关键作用。
Proper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment. This function is independent of mDia3 actin nucleation activity, but is attributable to EB1-binding by mDia3. Furthermore, the microtubule binding FH2 domain of mDia3 is phosphorylated by Aurora B kinase in vitro, and cells expressing the nonphosphorylatable mDia3 mutant cannot position chromosomes at the metaphase plate. Purified recombinant mDia3 phosphorylated by Aurora B exhibits reduced ability to bind microtubules and stabilize microtubules against cold-induced disassembly in vitro. Cells expressing the phosphomimetic mDia3 mutant do not form stable kinetochore microtubule fibers; despite they are able to congress chromosomes to the metaphase plate. These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment.