A nucleoporin that facilitates meiotic kinetochore reorganization
A nucleoporin that facilitates meiotic kinetochore reorganization
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DOI：
10.1080/15384101.2015.1125237
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发表时间：
2016-01
期刊：
影响因子：
4.3
通讯作者：
Hui-Ju Yang;T. Haraguchi;Y. Hiraoka
中科院分区：
文献类型：
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作者：
Hui-Ju Yang;T. Haraguchi;Y. Hiraoka
减数分裂是有性生殖生物产生单倍体配子的重要过程。减数分裂有效地将基因组倍性减少一半，涉及一轮染色体复制，然后是减数分裂 I 和减数分裂 II 中的 2 轮染色体分离。减数分裂 I 中的染色体分离与有丝分裂和减数分裂 II 中的染色体分离不同，同源染色体分离，但姐妹染色单体保持附着。减数分裂 I 中姐妹染色单体的提前分离是导致染色体疾病（例如三体疾病）的主要机制的基础。为了确保减数分裂 I 中姐妹染色单体的共分离，着丝粒在姐妹着丝粒处进行重组，以便姐妹着丝粒接收来自相同纺锤体极的微管（即单极纺锤体-着丝粒附着）。然而，控制姐妹动粒重组的机制尚未详细阐明。我们最近发现核孔复合体 (NPC) 成分 Nup132 参与调节裂殖酵母裂殖酵母中减数分裂着丝粒的组装。粟酒裂殖酵母优先通过有丝分裂繁殖，但在营养限制的条件下会进入减数分裂。当细胞从有丝分裂细胞周期过渡到减数分裂时，染色体动态地重新排列。在有丝分裂细胞中，着丝粒与酵母微管组织中心纺锤体极体（SPB）稳定结合，端粒远离 SPB。另一方面，进入减数分裂后，端粒被带到 SPB 并释放着丝粒。着丝粒和 SPB 的关联是通过 KMN (KNL1/Spc7Mis12-Nuf2) 复合物和 Csi1 之间的相互作用发生的。 Csi1 是一种 SPB 关联蛋白，而 KMN 复合体构成着丝粒的外部动粒，并在酵母的整个有丝分裂细胞周期中保持组装状态。然而，在减数分裂早期，Csi1 和 KMN 复合体分别从 SPB 和着丝粒上解体（图 1）。如果 KMN 复合体和 Csi1 之间没有相互作用，着丝粒可以在早期减数分裂前期从 SPB 中释放出来。在前期后期，Csi1 与 SPB 重新结合。与此同时，KMN 复合物在着丝粒处重新组装，并促进着丝粒在 SPB 处重新捕获。在 nup132D 突变体中，Csi1 与 SPB 的动态关联正常发生；然而，这种突变会影响着丝粒处 KMN 复合体的组装。在 nup132D 突变体中，KMN 组件 Mis12 和 Spc7 停留在减数分裂前期的着丝粒上，而 KMN 复合物通常在野生型细胞中分解。具有预组装的 Mis12 和 Spc7 的着丝粒在减数分裂前期早期仍与 SPB 分离，可能是因为 Nuf2-Ndc80 复合体直到减数分裂前期后期才并入 KMN 复合体。纺锤体组装检查点 (SAC) 成分 Bub1 也被提前招募到前期着丝粒。这种预组装的着丝粒随后影响 nup132D 突变体第一次减数分裂时的微管-着丝粒附着。通过对着丝粒沿减数分裂纺锤体行为的活细胞成像，我们发现在nup132D突变体中，姐妹着丝粒在纺锤体两极之间不稳定地移动。相反，由于减数分裂I中的单极纺锤体-着丝粒附着，在正常情况下，姐妹着丝粒通常稳定地一起朝着同一纺锤体极移动。这些结果表明，nup132D突变体的姐妹着丝粒在减数分裂I中接收来自相反纺锤体极的微管。因此，不适当的微管-着丝粒附着激活SAC并导致减数分裂I延长。SAC的激活有助于纠正错误的微管-着丝粒附着，使得姐妹染色单体在减数分裂中仍然以高保真度共分离。我是nup132D突变体。尽管如此，在缺少 SAC 成分 Mad2 或 Bub1 的情况下，nup132D 突变体中减数分裂 I 的延长时间缩短，姐妹染色单体早熟分离的频率增加。奇怪的是，我们发现姐妹染色单体在 nup132Dbub1D 双突变体中几乎是随机分离的。除了 SAC 之外，Bub1 还具有将粘连蛋白保护蛋白 Sgo1 募集到着丝粒区域的功能。然而，nup132D 和 bub1D 在姐妹染色单体分离中的协同效应并不仅仅因为 Sgo1 的丢失而发生，因为
Meiosis is an important process for sexually reproducing organisms to generate haploid gametes. Meiosis effectively reduces the genome ploidy by half, involving one round of chromosome replication followed by 2 rounds of chromosome segregation in meiosis I and meiosis II. Chromosome segregation in meiosis I differs from that in mitosis and meiosis II, in that homologous chromosomes segregate but sister chromatids remain attached. Precocious separation of sister chromatids in meiosis I underlies the main mechanism contributing to chromosomal disorders such as trisomy diseases. In order to ensure co-segregation of the sister chromatids in meiosis I, the kinetochores are reorganized at the sister centromeres so that sister kinetochores receive microtubules from the same spindle poles (i.e., monopolar spindle-kinetochore attachment). However, the mechanism contributing to the control of sister kinetochore reorganization has not yet been elucidated in detail. We recently found that a nuclear pore complex (NPC) component, Nup132, is involved in regulating meiotic kinetochore assembly in the fission yeast Schizosaccharomyces pombe. S. pombe preferentially reproduces through mitosis but will enter meiosis under conditions of nutrient limitation. The chromosomes are dynamically rearranged as the cells transit from the mitotic cell cycle to meiosis. In mitotic cells, the centromeres stably associate with the spindle pole body (SPB), the yeast microtubule-organizing center, and the telomeres are distant from the SPB. On the other hand, upon entry into meiosis, the telomeres are brought toward the SPB and the centromeres are released. Association of the centromeres and the SPB occurs through interactions between the KMN (KNL1/Spc7Mis12-Nuf2) complex and Csi1. Csi1 is an SPB-association protein, whereas the KMN complex constitutes the outer kinetochores at the centromeres and remains assembled throughout the mitotic cell cycles in yeasts. However, in early meiosis, Csi1 and the KMN complex disassemble from the SPB and the centromeres, respectively (Fig. 1). Without interactions between the KMN complex and Csi1, the centromeres can be liberated from the SPB in early meiotic prophase. In late prophase, Csi1 re-associates with the SPB. Concomitantly, the KMN complex reassembles at the centromeres and facilitates centromere recapture at the SPB. In the nup132D mutant, dynamic association of Csi1 to the SPB occurs as normal; however, this mutation impacts assembly of the KMN complex at the centromeres. The KMN components Mis12 and Spc7 stay at the centromeres in early meiotic prophase in the nup132Dmutant, while the KMN complex normally disassembles in the wild-type cells. The centromeres with preassembled Mis12 and Spc7 remain detached from the SPB in early meiotic prophase, possibly because the Nuf2-Ndc80 complex is not incorporated into the KMN complex until late meiotic prophase. The spindle assembly checkpoint (SAC) component Bub1 is also precociously recruited to the prophase centromeres. This preassembled kinetochore subsequently affects the microtubule-kinetochore attachments at the first meiotic division in the nup132D mutant. Through livecell imaging of the behaviors of the centromere along the meiotic spindles, we found that the sister centromeres unsteadily move between the spindle poles in the nup132D mutant. In contrast, due to monopolar spindle-kinetochore attachment in meiosis I, the sister centromeres usually steadily move together toward the same spindle pole in the normal condition. These results indicate that the sister kinetochores of the nup132D mutant receive microtubules from the opposite spindle poles in meiosis I. Thus, inappropriate microtubule-kinetochore attachment activates the SAC and results in prolongation of meiosis I. Activation of the SAC facilitates correction of the erroneous microtubule-kinetochore attachment, so that the sister chromatids still co-segregate with high fidelity in meiosis I in the nup132D mutant. Nonetheless, in the absence of the SAC component Mad2 or Bub1, the prolongation of meiosis I is shortened, and the frequency of precocious sister chromatid segregation is increased in the nup132D mutant. Curiously, sister chromatids were found to segregate almost randomly in the nup132Dbub1D double mutant. In addition to the SAC, Bub1 also functions in recruiting the cohesin protector Sgo1 to the centromeric region. However, the synergistic effects of nup132D and bub1D in sister chromatid segregation do not simply occur because of the loss of Sgo1, given that