Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing protein (MISS), a new MAPK substrate.
Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing protein (MISS), a new MAPK substrate.
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DOI：
10.1083/jcb.200202052
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发表时间：
2002-05-13
期刊：
影响因子：
--
通讯作者：
Verlhac MH
中科院分区：
文献类型：
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作者：
Lefebvre C;Terret ME;Djiane A;Rassinier P;Maro B;Verlhac MH
脊椎动物卵母细胞在减数分裂的第二个中期（中期II [MII]）被称为细胞生长抑制因子（CSF）的活性所阻滞，具有对齐的染色体和稳定的纺锤体。染色体的分离发生在受精后。Mos/.../MAPK（丝裂原活化蛋白激酶）途径介导这种MII停滞。利用双杂交筛选，我们确定了一个新的MAPK合作伙伴从小鼠卵母细胞cDNA文库。这种蛋白质在第一次减数分裂期间是不稳定的，并且仅在MII中积累，在那里它定位于纺锤体。它是Mos/.../MAPK途径的底物。通过三种不同的方式（反义RNA，双链[ds] RNA，或吗啉代寡核苷酸）的内源性RNA编码这种蛋白质的耗竭诱导严重的纺锤体缺陷特定于MII卵母细胞。从没有被吗啉代靶向的RNA过表达蛋白质拯救了纺锤体不稳定。然而，dsRNA对前两次有丝分裂没有影响。因此，我们发现了一种新的MAPK底物，在小鼠卵母细胞的CSF停滞过程中参与维持纺锤体的完整性，称为MISS（MAP激酶相互作用和纺锤体稳定蛋白）。
Vertebrate oocytes arrest in the second metaphase of meiosis (metaphase II [MII]) by an activity called cytostatic factor (CSF), with aligned chromosomes and stable spindles. Segregation of chromosomes occurs after fertilization. The Mos/…/MAPK (mitogen-activated protein kinases) pathway mediates this MII arrest. Using a two-hybrid screen, we identified a new MAPK partner from a mouse oocyte cDNA library. This protein is unstable during the first meiotic division and accumulates only in MII, where it localizes to the spindle. It is a substrate of the Mos/…/MAPK pathway. The depletion of endogenous RNA coding for this protein by three different means (antisense RNA, double-stranded [ds] RNA, or morpholino oligonucleotides) induces severe spindle defects specific to MII oocytes. Overexpressing the protein from an RNA not targeted by the morpholino rescues spindle destabilization. However, dsRNA has no effect on the first two mitotic divisions. We therefore have discovered a new MAPK substrate involved in maintaining spindle integrity during the CSF arrest of mouse oocytes, called MISS (for MAP kinase–interacting and spindle-stabilizing protein).