Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient
Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient
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DOI：
10.1038/nature06923
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发表时间：
2008-06-19
期刊：
影响因子：
64.8
通讯作者：
Kapoor, Tarun M.
中科院分区：
文献类型：
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作者：
Fuller, Brian G.;Lampson, Michael A.;Kapoor, Tarun M.
在两个子细胞之间适当划分细胞内容需要空间和时间线索的整合。在纺锤体中部自组织的后期微管阵列有助于将细胞分裂平面定位在分离的染色体之间(1)。这种信号是如何在微米尺度上发生的，从中间区域到细胞皮层，目前还不清楚。在这里，我们使用基于荧光共振能量转移（FRET）的传感器和天然极光B底物的免疫荧光，研究了有丝分裂关键调节剂极光B激酶磷酸化的后期动力学。使用染色体和着丝粒靶向传感器对磷酸化动力学进行定量分析，揭示了变化主要是由于沿分裂轴的位置而不是时间。这些动态导致在后期早期形成以纺锤体中部为中心的空间磷酸化梯度。这种梯度取决于极光B靶向激活它的微管亚群。极光激酶活性组织目标微管以产生基于结构的反馈回路。我们提出极光B激酶激活和中间区微管之间的反馈产生了翻译后标记的梯度，为后期和细胞质分裂事件提供了空间信息。
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(1). 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.