The Drosophila NuMA homolog mud regulates spindle orientation in asymmetric cell division
The Drosophila NuMA homolog mud regulates spindle orientation in asymmetric cell division
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DOI：
10.1016/j.devcel.2006.05.005
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发表时间：
2006-06-01
影响因子：
11.8
通讯作者：
Knoblich, Juergen A.
中科院分区：
文献类型：
--
作者：
Bowman, Sarah K.;Neumueller, Ralph A.;Knoblich, Juergen A.
在不对称细胞分裂过程中，有丝分裂纺锤体必须正确定向，以确保细胞命运决定因子不对称分离到两个子细胞中的一个。在果蝇神经母细胞中，纺锤体取向需要异源三聚体G蛋白和G α结合伴侣Pins，但Pins-G α i复合物如何与有丝分裂纺锤体相互作用尚不清楚。在这里，我们表明，引脚直接结合微管结合蛋白泥，果蝇同源的NuMA。与NuMA一样，Mud可以与微管结合并增强微管聚合。在没有Mud的情况下，果蝇成神经细胞的有丝分裂纺锤体不能与极性轴对齐。这可能导致细胞命运决定因子Brat和Prospero的对称分离，导致果蝇神经系统中子代细胞命运的错误指定和肿瘤样过度增殖。我们的数据表明，在该模型中，不对称本地化的Pins-Gai复合物调节主轴方向直接绑定到泥。
During asymmetric cell division, the mitotic spindle must be properly oriented to ensure the asymmetric segregation of cell fate determinants into only one of the two daughter cells. In Drosophila neuroblasts, spindle orientation requires heterotrimeric G proteins and the G alpha binding partner Pins, but how the Pins-G alpha i complex interacts with the mitotic spindle is unclear. Here, we show that Pins binds directly to the microtubule binding protein Mud, the Drosophila homolog of NuMA. Like NuMA, Mud can bind to microtubules and enhance microtubule polymerization. In the absence of Mud, mitotic spindles in Drosophila neuroblasts fail to align with the polarity axis. This can lead to symmetric segregation of the cell fate determinants Brat and Prospero, resulting in the misspeclfication of daughter cell fates and tumor-like overproliferation in the Drosophila nervous system. Our data suggest a model in which asymmetrically localized Pins-Gai complexes regulate spindle orientation by directly binding to Mud.