The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4
The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4
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DOI：
10.1091/mbc.e16-04-0219
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发表时间：
2016-10-15
影响因子：
3.3
通讯作者：
Skop, Ahna R.
中科院分区：
文献类型：
--
作者：
Gnazzo, Megan M.;Uhlemann, Eva-Maria E.;Skop, Ahna R.
纺锤体中部含有微管和蛋白质，这些都是沟槽形成和细胞质分裂完成所必需的。然而，细胞分裂因子在时间和空间上募集到纺锤体中区和中体的机制尚不清楚。在这里，我们描述了一种由保守的RNA结合蛋白ATX-2/Aaxin-2控制的机制，该蛋白以纺锤体中区为靶点并维持Zen-4。ATX-2通过调节有丝分裂结构，特别是纺锤体、中心体和中体的PAR-5的数量来做到这一点。阻止ATX-2功能导致PAR-5水平升高，PAR-5-GFP染色质和中心体定位增强，最终导致纺锤体中区Zen-4-GFP减少。ATX-2和PAR-5的缺失挽救了Zen-4在纺锤体中段的定位，表明ATX-2介导了Zen-4在PAR-5上游的定位。我们提供了ATX-2对胞质分裂是必需的第一个直接证据，并提出了一个模型，在该模型中，ATX-2通过介导PAR-5的转录后调控，促进了Zen-4对纺锤体中区的靶向。
The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5.