Arl2- and Msps-dependent microtubule growth governs asymmetric division.
Arl2- and Msps-dependent microtubule growth governs asymmetric division.
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DOI：
10.1083/jcb.201503047
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发表时间：
2016-03-14
期刊：
影响因子：
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通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Chen K;Koe CT;Xing ZB;Tian X;Rossi F;Wang C;Tang Q;Zong W;Hong WJ;Taneja R;Yu F;Gonzalez C;Wu C;Endow S;Wang H
果蝇Arl 2通过调控微管生长和Msps定位于中心体来控制成神经细胞的不对称分裂。神经干细胞的不对称分裂是平衡其自我更新和分化的基本策略。长期以来，人们认为微管对于不对称分裂的果蝇成神经细胞（NBs;神经干细胞）的细胞极性不是必需的。在这里，我们表明，果蝇ADP核糖基化因子样-2（Arl 2）和Msps，一个已知的微管结合蛋白，控制细胞极性和纺锤体方向的NB。在arl 2 RNA干扰、Arl 2-GDP表达或arl 2缺失后，观察到微管异常和不对称分裂缺陷。相反，Arl 2的过度活化导致微管过度生长和NB的耗尽。Arl 2通过将Msps定位于NB中的中心体来调节微管生长和不对称分裂。此外，Arl 2调节动力蛋白功能，进而调节D-TACC和Msps的中心体定位。Arl 2与微管蛋白辅因子C、D和E物理结合。Arl 2与微管蛋白结合辅因子D一起起作用以控制微管生长、Msps定位和NB自我更新。因此，Arl 2和Msps依赖的微管生长是调节神经干细胞不对称分裂的新范式。
Drosophila Arl2 governs neuroblast asymmetric cell division through regulation of microtubule growth and localization of Msps to centrosomes. Asymmetric division of neural stem cells is a fundamental strategy to balance their self-renewal and differentiation. It is long thought that microtubules are not essential for cell polarity in asymmetrically dividing Drosophila melanogaster neuroblasts (NBs; neural stem cells). Here, we show that Drosophila ADP ribosylation factor like-2 (Arl2) and Msps, a known microtubule-binding protein, control cell polarity and spindle orientation of NBs. Upon arl2 RNA intereference, Arl2-GDP expression, or arl2 deletions, microtubule abnormalities and asymmetric division defects were observed. Conversely, overactivation of Arl2 leads to microtubule overgrowth and depletion of NBs. Arl2 regulates microtubule growth and asymmetric division through localizing Msps to the centrosomes in NBs. Moreover, Arl2 regulates dynein function and in turn centrosomal localization of D-TACC and Msps. Arl2 physically associates with tubulin cofactors C, D, and E. Arl2 functions together with tubulin-binding cofactor D to control microtubule growth, Msps localization, and NB self-renewal. Therefore, Arl2- and Msps-dependent microtubule growth is a new paradigm regulating asymmetric division of neural stem cells.