Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization
Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization
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DOI：
10.1038/ncb1409
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发表时间：
2006-06-01
影响因子：
21.3
通讯作者：
Matsuzaki, Fumio
中科院分区：
文献类型：
--
作者：
Izumi, Yasushi;Ohta, Nao;Matsuzaki, Fumio
有丝分裂纺锤体相对于细胞轴的方向决定了极化细胞是否经历对称或不对称分裂。果蝇上皮细胞和成神经细胞提供了一对理想的细胞来研究相关的调节机制。上皮细胞垂直于顶基轴对称分裂。相比之下，在成神经细胞的不对称分裂中，纺锤体平行于该轴重新定向，导致细胞命运决定因素不均匀地分配给一个子细胞（1）。涉及GoLoco蛋白Pins的受体非依赖性G蛋白信号传导对于两种细胞类型中的纺锤体方向至关重要（2）。在这里，我们确定蘑菇体缺陷（Mud）3作为该途径的下游效应子。在成神经细胞和上皮细胞中，Mud直接与覆盖纺锤体极的细胞皮质处的Pin结合并共定位。皮质Mud蛋白在两种不同的分裂模式中对正确的纺锤体方向是必不可少的。此外，在有丝分裂期间，Mud独立于Pin定位于中心体以调节中心体组织。我们认为果蝇Mud、脊椎动物NuMA（4）和秀丽隐杆线虫Lin-5（参考文献5，6）在G蛋白调节有丝分裂纺锤体的机制中具有保守的作用。
The orientation of the mitotic spindle relative to the cell axis determines whether polarized cells undergo symmetric or asymmetric divisions. Drosophila epithelial cells and neuroblasts provide an ideal pair of cells to study the regulatory mechanisms involved. Epithelial cells divide symmetrically, perpendicular to the apical-basal axis. In the asymmetric divisions of neuroblasts, by contrast, the spindle reorients parallel to that axis, leading to the unequal distribution of cell-fate determinants to one daughter cell(1). Receptor-independent G-protein signalling involving the GoLoco protein Pins is essential for spindle orientation in both cell types(2). Here, we identify Mushroom body defect ( Mud) 3 as a downstream effector in this pathway. Mud directly associates and colocalizes with Pins at the cell cortex overlying the spindle pole(s) in both neuroblasts and epithelial cells. The cortical Mud protein is essential for proper spindle orientation in the two different division modes. Moreover, Mud localizes to centrosomes during mitosis independently of Pins to regulate centrosomal organization. We propose that Drosophila Mud, vertebrate NuMA(4) and Caenorhabditis elegans Lin-5 (refs 5, 6) have conserved roles in the mechanism by which G-proteins regulate the mitotic spindle.