Twins/PP2A regulates aPKC to control neuroblast cell polarity and self-renewal
Twins/PP2A regulates aPKC to control neuroblast cell polarity and self-renewal
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DOI：
10.1016/j.ydbio.2009.04.014
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发表时间：
2009-06-15
影响因子：
2.7
通讯作者：
Doe, Chris Q.
中科院分区：
文献类型：
--
作者：
Chabu, Chiswili;Doe, Chris Q.
在果蝇和哺乳动物中，不对称细胞分裂是产生细胞多样性和维持干细胞动态平衡的一种机制。在果蝇中，幼虫神经母细胞是类似干细胞的前体细胞，不对称分裂，生成成年大脑的神经元。有丝分裂的神经母细胞将非典型蛋白激酶C(APKC)定位于顶叶皮质。皮质aPKC排除了Miranda及其货物蛋白Propero和脑瘤的皮质定位，导致它们分裂成分化中的更小的神经节母细胞(GMC)，在那里它们是神经元分化所必需的。除了蛋白激酶C外，Aurora-A和Polo也调节神经母细胞的自我更新，但参与神经母细胞自我更新的磷酸酶尚未确定。在这里，我们报道了aPKC在体内与双胞胎的蛋白质复合体，双胞胎是果蝇B型蛋白磷酸酶2A(PP2A)的一个亚单位，在幼虫神经母细胞中检测到双胞胎和PP2A的催化亚基，称为微管星形(MTS)。双胞胎和MTS都需要从基底神经母细胞皮质中排除aPKC：双胞胎突变脑、双胞胎突变单个神经母细胞突变克隆或MTS显性阴性单个神经母细胞克隆都显示出aPKC在基底皮质中的异位定位。与异位基础aPKC一致的是，在双胞胎突变脑或双胞胎突变克隆中出现了额外的神经母细胞。我们的结论是，TWINS/PP2A需要维持有丝分裂成神经母细胞顶端皮质的PKC，使其远离分化的公民细胞，从而维持神经母细胞的动态平衡。(C)2009 Elsevier Inc.保留所有权利。
Asymmetric cell division is a mechanism for generating cell diversity as well as maintaining stem cell homeostasis in both Drosophila and mammals. In Drosophila, larval neuroblasts are stem cell-like progenitors that divide asymmetrically to generate neurons of the adult brain. Mitotic neuroblasts localize atypical protein kinase C (aPKC) to their apical cortex. Cortical aPKC excludes cortical localization of Miranda and its cargo proteins Prospero and Brain tumor, resulting in their partitioning into the differentiating, smaller ganglion mother cell (GMC) where they are required for neuronal differentiation. In addition to aPKC, the kinases Aurora-A and Polo also regulate neuroblast self-renewal, but the phosphatases involved in neuroblast self-renewal have not been identified. Here we report that aPKC is in a protein complex in vivo with Twins, a Drosophila B-type protein phosphatase 2A (PP2A) subunit, and that Twins and the catalytic subunit of PP2A, called Microtubule star (Mts), are detected in larval neuroblasts. Both Twins and Mts are required to exclude aPKC from the basal neuroblast cortex: twins mutant brains, twins mutant single neuroblast mutant clones, or mts dominant negative single neuroblast clones all show ectopic basal cortical localization of aPKC. Consistent with ectopic basal aPKC is the appearance of supernumerary neuroblasts in twins mutant brains or twins mutant clones. We conclude that Twins/PP2A is required to maintain aPKC at the apical cortex of mitotic neuroblasts, keeping it out of the differentiating CIVIC, and thereby maintaining neuroblast homeostasis. (C) 2009 Elsevier Inc. All rights reserved.