The Microcephaly-Associated Protein Wdr62/CG7337 Is Required to Maintain Centrosome Asymmetry in Drosophila Neuroblasts
The Microcephaly-Associated Protein Wdr62/CG7337 Is Required to Maintain Centrosome Asymmetry in Drosophila Neuroblasts
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DOI：
10.1016/j.celrep.2015.12.097
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发表时间：
2016-02-09
期刊：
影响因子：
8.8
通讯作者：
Cabernard, Clemens
中科院分区：
文献类型：
--
作者：
Nair, Anjana Ramdas;Singh, Priyanka;Cabernard, Clemens
中心体的不对称性与果蝇和脊椎动物的干细胞命运维持有关，但其潜在的分子机制尚不完全清楚。在这里，我们报告说，损失CG 7337，飞直系同源的WDR 62，妥协间期中心体不对称的苍蝇神经干细胞（神经母细胞）。Wdr 62通过稳定微管（MT）来维持活跃的间期微管组织中心（MTOC），这对于将波罗/Plk 1持续募集到中心周围基质（PCM）和下调中心周围蛋白样蛋白（Plp）是必需的。wdr 62突变体中活性MTOC的丧失损害了中心体定位、纺锤体取向和偏中心体分离。由于细胞周期延迟，WDR 62突变果蝇的脑大小也减少了约40%。我们建议，CG 7337/Wdr 62，微管相关蛋白，需要为间期微管的维护，从而调节中心体波罗和PLP水平。独立于此功能，Wdr 62也需要及时有丝分裂进入神经干细胞。
Centrosome asymmetry has been implicated in stem cell fate maintenance in both flies and vertebrates, but the underlying molecular mechanisms are incompletely understood. Here, we report that loss of CG7337, the fly ortholog of WDR62, compromises interphase centrosome asymmetry in fly neural stem cells (neuroblasts). Wdr62 maintains an active interphase microtubule-organizing center (MTOC) by stabilizing microtubules (MTs), which are necessary for sustained recruitment of Polo/Plk1 to the pericentriolar matrix (PCM) and downregulation of Pericentrin-like protein (Plp). The loss of an active MTOC in wdr62 mutants compromises centrosome positioning, spindle orientation, and biased centrosome segregation. wdr62 mutant flies also have an similar to 40% reduction in brain size as a result of cell-cycle delays. We propose that CG7337/Wdr62, a microtubule-associated protein, is required for the maintenance of interphase microtubules, thereby regulating centrosomal Polo and Plp levels. Independent of this function, Wdr62 is also required for the timely mitotic entry of neural stem cells.