Drosophila Mbm Is a Nucleolar Myc and Casein Kinase 2 Target Required for Ribosome Biogenesis and Cell Growth of Central Brain Neuroblasts
Drosophila Mbm Is a Nucleolar Myc and Casein Kinase 2 Target Required for Ribosome Biogenesis and Cell Growth of Central Brain Neuroblasts
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DOI：
10.1128/mcb.00658-13
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发表时间：
2014-05-01
影响因子：
5.3
通讯作者：
Raabe, Thomas
中科院分区：
文献类型：
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作者：
Hovhanyan, Anna;Herter, Eva K.;Raabe, Thomas
适当的细胞生长是维持细胞反复分裂的先决条件。细胞需要将有关细胞内营养物质可用性和来自能量感应器官的生长线索的信息转化为促进生长的过程，例如为蛋白质合成提供足够的核糖体供应。蘑菇体微型 (mbm) 基因的突变会损害果蝇中枢神经祖细胞（神经母细胞）的增殖。然而迄今为止，Mbm 的分子功能尚不清楚。在这里，我们证明 mbm 不会影响控制神经母细胞不对称细胞分裂的分子机制，而是会减小其细胞大小。 Mbm 是神经母细胞中小核糖体亚基生物发生所需的核仁蛋白。因此，mbm 神经母细胞中的蛋白质合成水平降低。 Mbm 表达受 Myc 转录调节，除其他功能外，Myc 将信息从营养依赖性信号传导途径传递到核糖体基因表达。在翻译后水平，Mbm 被酪蛋白激酶 2 (CK2) 磷酸化，这对该蛋白的定位产生影响。我们得出的结论是，Mbm 是参与核糖体生物合成的 Myc 靶网络的新部分，它与 CK2 介导的信号一起使神经母细胞能够合成适当细胞生长所需的足够量的蛋白质。
Proper cell growth is a prerequisite for maintaining repeated cell divisions. Cells need to translate information about intracellular nutrient availability and growth cues from energy-sensing organs into growth-promoting processes, such as sufficient supply with ribosomes for protein synthesis. Mutations in the mushroom body miniature (mbm) gene impair proliferation of neural progenitor cells (neuroblasts) in the central brain of Drosophila melanogaster. Yet the molecular function of Mbm has so far been unknown. Here we show that mbm does not affect the molecular machinery controlling asymmetric cell division of neuroblasts but instead decreases their cell size. Mbm is a nucleolar protein required for small ribosomal subunit biogenesis in neuroblasts. Accordingly, levels of protein synthesis are reduced in mbm neuroblasts. Mbm expression is transcriptionally regulated by Myc, which, among other functions, relays information from nutrient-dependent signaling pathways to ribosomal gene expression. At the posttranslational level, Mbm becomes phosphorylated by casein kinase 2 (CK2), which has an impact on localization of the protein. We conclude that Mbm is a new part of the Myc target network involved in ribosome biogenesis, which, together with CK2-mediated signals, enables neuroblasts to synthesize sufficient amounts of proteins required for proper cell growth.