Extrinsic cues, intrinsic cues and microfilaments regulate asymmetric protein localization in Drosophila neuroblasts
Extrinsic cues, intrinsic cues and microfilaments regulate asymmetric protein localization in Drosophila neuroblasts
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DOI：
10.1016/s0960-9822(06)00370-8
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发表时间：
1997-11-01
期刊：
影响因子：
9.2
通讯作者：
Doe, CQ
中科院分区：
文献类型：
--
作者：
Broadus, J;Doe, CQ
背景资料：果蝇的中枢神经系统是从称为神经母细胞的干细胞样前体细胞发育而来的，神经母细胞不均匀地分裂成一系列较小的子细胞，称为神经节母细胞。成神经细胞显示细胞周期特异性的RNA和蛋白质的不对称定位：在后期间期，Prospero RNA和Inscuteable，Prospero和Staufen蛋白都位于顶端;在有丝分裂，Inscuteable仍然是顶端，而Prospero RNA，Prospero蛋白和Staufen蛋白形成基底皮质新月形。在这里，我们使用在体外培养的神经母细胞调查的作用，内在和外在的线索和细胞骨架中的不对称本地化的Insuteable，Prospero和Staufen proteins.Results：神经母细胞胞质分裂是正常的在体外，产生一个较大的神经母细胞和一个较小的神经节母细胞。在体外减少或消除间期成神经细胞中的Inscuteable、Prospero和Staufen的顶端定位，但所有三种蛋白质在有丝分裂期间正常定位（顶端Inscuteable、基底Prospero和Staufen）。微丝抑制剂导致所有三种蛋白质的离域。在皮质中不可见变得均匀，而普洛斯彼罗和Staufen成为细胞质;抑制剂洗脱导致恢复的微丝和所有三种蛋白质的不对称定位。微管破坏对蛋白定位没有影响，但微管和微丝的破坏导致在细胞质定位的Insuteable.Conclusions：外在和内在的线索调节蛋白定位在成神经细胞。微丝，而不是微管，是必不可少的不对称蛋白质锚定（和可能的本地化）在有丝分裂神经母细胞。我们的研究结果突出了果蝇，秀丽隐杆线虫，脊椎动物，植物和酵母之间的相似性：在所有生物体中，不对称的蛋白质或RNA定位和/或锚定需要微丝。
Background: The Drosophila central nervous system develops from stem cell like precursors called neuroblasts, which divide unequally to bud off a series of smaller daughter cells called ganglion mother cells. Neuroblasts show cell-cycle-specific asymmetric localization of both RNA and proteins: at late interphase, prospero RNA and Inscuteable, Prospero and Staufen proteins are all apically localized; at mitosis, Inscuteable remains apical whereas prospero RNA, Prospero protein and Staufen protein form basal cortical crescents. Here we use in vitro culture of neuroblasts to investigate the role of intrinsic and extrinsic cues and the cytoskeleton in asymmetric localization of Inscuteable, Prospero and Staufen proteins.Results: Neuroblast cytokinesis is normal in vitro, producing a larger neuroblast and a smaller ganglion mother cell. Apical localization of Inscuteable, Prospero and Staufen in interphase neuroblasts is reduced or eliminated in vitro, but all three proteins are localized normally during mitosis (apical Inscuteable, basal Prospero and Staufen). Microfilament inhibitors result in delocalization of all three proteins. Inscuteable becomes uniform at the cortex, whereas Prospero and Staufen become cytoplasmic; inhibitor washout leads to recovery of microfilaments and asymmetric localization of all three proteins. Microtubule disruption has no effect on protein localization, but disruption of both microtubules and microfilaments results in cytoplasmic localization of Inscuteable.Conclusions: Both extrinsic and intrinsic cues regulate protein localization in neuroblasts. Microfilaments, but not microtubules, are essential for asymmetric protein anchoring (and possibly localization) in mitotic neuroblasts. Our results highlight the similarity between Drosophila, Caenorhabditis elegans, vertebrates, plants and yeast: in all organisms, asymmetric protein or RNA localization and/or anchoring requires microfilaments.