14-3-3 regulation of Ncd reveals a new mechanism for targeting proteins to the spindle in oocytes.
14-3-3 regulation of Ncd reveals a new mechanism for targeting proteins to the spindle in oocytes.
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DOI：
10.1083/jcb.201704120
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发表时间：
2017-10-02
期刊：
影响因子：
--
通讯作者：
Ohkura H
中科院分区：
文献类型：
--
作者：
Beaven R;Bastos RN;Spanos C;Romé P;Cullen CF;Rappsilber J;Giet R;Goshima G;Ohkura H
14-3-3与驱动蛋白-14 Ncd相互作用并阻止其结合微管。Aurora B提供了一个空间线索，从染色体周围的14-3-3释放Ncd，使Ncd选择性地结合大量卵母细胞中的纺锤体微管。在大量卵母细胞中形成的纺锤体不含中心体。在卵母细胞中，染色体周围的关键纺锤体蛋白的局部激活对于双极纺锤体的形成和维持是重要的。我们发现，磷酸对接14-3-3蛋白质稳定纺锤体双极性在果蝇卵母细胞。一个关键的14-3-3目标是负端定向运动Ncd（人HSET;驱动蛋白-14），它在稳定卵母细胞中的双极纺锤体中具有良好的记录作用。通过14-3-3的磷酸对接抑制非运动Ncd尾的微管结合活性。极光B激酶的进一步磷酸化可以从14-3-3的这种抑制作用中释放Ncd。由于Aurora B定位于染色体和纺锤体，14-3-3通过阻止Ncd与卵母细胞中非纺锤体微管结合，促进Ncd与纺锤体微管的特异性结合。因此，14-3-3将Aurora B提供的空间提示翻译为选择性地将Ncd靶向大体积卵母细胞内的纺锤体。
14-3-3 interacts with the kinesin-14 Ncd and prevents it from binding microtubules. Aurora B provides a spatial cue that releases Ncd from 14-3-3 around chromosomes, allowing Ncd to selectively bind the spindle microtubules in the large volume of oocytes. The meiotic spindle is formed without centrosomes in a large volume of oocytes. Local activation of crucial spindle proteins around chromosomes is important for formation and maintenance of a bipolar spindle in oocytes. We found that phosphodocking 14-3-3 proteins stabilize spindle bipolarity in Drosophila melanogaster oocytes. A critical 14-3-3 target is the minus end–directed motor Ncd (human HSET; kinesin-14), which has well-documented roles in stabilizing a bipolar spindle in oocytes. Phospho docking by 14-3-3 inhibits the microtubule binding activity of the nonmotor Ncd tail. Further phosphorylation by Aurora B kinase can release Ncd from this inhibitory effect of 14-3-3. As Aurora B localizes to chromosomes and spindles, 14-3-3 facilitates specific association of Ncd with spindle microtubules by preventing Ncd from binding to nonspindle microtubules in oocytes. Therefore, 14-3-3 translates a spatial cue provided by Aurora B to target Ncd selectively to the spindle within the large volume of oocytes.
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