The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts
The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts
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DOI：
10.1038/ncb1412
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发表时间：
2006-06-01
影响因子：
21.3
通讯作者：
Doe, Chris Q.
中科院分区：
文献类型：
--
作者：
Siller, Karsten H.;Cabernard, Clemens;Doe, Chris Q.
不对称细胞分裂在发育过程中产生细胞多样性（1，2），并调节果蝇和哺乳动物的干细胞自我更新（3，4）。在果蝇中，成神经细胞将它们的纺锤体与皮质伴侣Insuteable（Pins）-Gai新月体对齐以不对称地分裂，但皮质极性与有丝分裂纺锤体之间的联系知之甚少。在这里，我们表明，针直接结合，并与免疫共沉淀，NuMA相关的蘑菇体缺陷（泥）蛋白。Pins将Mud招募到成神经细胞的顶端皮质，并且Mud也以与NuMA类似的方式强烈定位于中心体/纺锤体极。在mud突变体中，皮质极性是正常的，但中期纺锤体经常无法与皮质极性轴对齐。当纺锤体方向与细胞极性正交时，发生对称分裂。我们建议，泥是哺乳动物的NuMA和秀丽隐杆线虫Lin-5的功能性直系同源物，并且泥协调纺锤体取向与皮质极性以促进不对称细胞分裂。
Asymmetric cell division generates cell diversity during development(1,2) and regulates stem-cell self-renewal in Drosophila and mammals(3,4). In Drosophila, neuroblasts align their spindle with a cortical Partner of Inscuteable (Pins)-Gai crescent to divide asymmetrically, but the link between cortical polarity and the mitotic spindle is poorly understood. Here, we show that Pins directly binds, and coimmunoprecipitates with, the NuMA-related Mushroom body defect (Mud) protein. Pins recruits Mud to the neuroblast apical cortex, and Mud is also strongly localized to centrosome/spindle poles, in a similar way to NuMA. In mud mutants, cortical polarity is normal, but the metaphase spindle frequently fails to align with the cortical polarity axis. When spindle orientation is orthogonal to cell polarity, symmetric division occurs. We propose that Mud is a functional orthologue of mammalian NuMA and Caenorhabditis elegans Lin-5, and that Mud coordinates spindle orientation with cortical polarity to promote asymmetric cell division.