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Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient

机译:后期极光B的中区激活产生细胞内磷酸化梯度

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摘要

Proper partitioning of the contents of a cell between two daughters requires integration of spatial and temporal cues. The anaphase array of microtubules that self-organize at the spindle midzone contributes to positioning the cell-division plane midway between the segregating chromosomes'. How this signalling occurs over length scales of micrometres, from the midzone to the cell cortex, is not known. Here we examine the anaphase dynamics of protein phosphorylation by aurora B kinase, a key mitotic regulator, using fluorescence resonance energy transfer (FRET)-based sensors in living HeLa cells and immunofluorescence of native aurora B substrates. Quantitative analysis of phosphorylation dynamics, using chromosome- and centromere-targeted sensors, reveals that changes are due primarily to position along the division axis rather than time. These dynamics result in the formation of a spatial phosphorylation gradient early in anaphase that is centred at the spindle midzone. This gradient depends on aurora B targeting to a subpopulation of microtubules that activate it. Aurora kinase activity organizes the targeted microtubules to generate a structure-based feedback loop. We propose that feedback between aurora B kinase activation and midzone microtubules generates a gradient of post-translational marks that provides spatial information for events in anaphase and cytokinesis.
机译:在两个子对象之间正确分配单元格内容需要整合空间和时间线索。在纺锤体中部自组织的微管的后期阵列有助于将细胞分裂平面定位在分离的染色体之间的中间。从中间区域到细胞皮层,这种信号传递如何在微米的长度尺度上发生是未知的。在这里,我们研究了活的HeLa细胞中基于荧光共振能量转移(FRET)的传感器和天然Aurora B底物的免疫荧光作用,通过关键的有丝分裂调节剂Aurora B激酶对蛋白质磷酸化的后期动力学进行了研究。使用针对染色体和着丝粒的传感器对磷酸化动力学进行定量分析,发现变化主要是由于沿分裂轴的位置而不是时间。这些动力学导致在后期早期形成以主轴中心区为中心的空间磷酸化梯度。该梯度取决于极光B靶向激活它的微管亚群。 Aurora激酶活性组织靶向的微管,以生成基于结构的反馈环。我们建议,极光B激酶激活和中区微管之间的反馈会生成一个梯度的翻译后标记,为后期和胞质分裂事件提供空间信息。

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  • 来源
    《Nature》 |2008年第7198期|1132-1136|共5页
  • 作者单位

    Departments of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA;

    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;

    Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York 10021, USA;

    Departments of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA;

    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;

    Departments of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA;

    Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA;

    Departments of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA;

    Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York 10021, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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