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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Op18 reveals the contribution of nonkinetochore microtubules to the dynamic organization of the vertebrate meiotic spindle
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Op18 reveals the contribution of nonkinetochore microtubules to the dynamic organization of the vertebrate meiotic spindle

机译:Op18揭示了非线粒体微管对脊椎动物减数分裂纺锤体动态组织的贡献。

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摘要

Accuracy in chromosome segregation depends on the assembly of a bipolar spindle. Unlike mitotic spindles, which have roughly equal amounts of kinetochore microtubules (kMTs) and nonkinetochore microtubules (non-kMTs), vertebrate meiotic spindles are predominantly comprised of non-kMTs, a large subset of which forms an antiparallel "barrel" array at the spindle equator. Though kMTs are needed to drive chromosome segregation, the contributions of non-kMTs are more mysterious. Here, we show that increasing the concentration of Op18/stathmin, a component of the chromosome-mediated microtubule formation pathway that directly controls mi-crotubule dynamics, can be used to deplete non-kMTs in the vertebrate meiotic spindle assembled in Xenopus egg extracts. Under these conditions, kMTs and the spindle pole-associated non-kMT arrays persist in smaller spindles. In excess Op18, distances between sister kinetochores, an indicator of tension across centromeres, remain unchanged, even though kMTs flux poleward with a ≈30% slower velocity, and chromosomes oscillate more than in control metaphase spindles. Remarkably, kinesin-5, a conserved motor protein that can push microtubules apart and is required for the assembly and maintenance of bipolar meiotic spindles, is not needed to maintain spindle bipolarity in the presence of excess Op18. Our data suggest that non-kMTs in meiotic spindles contribute to normal kMT dynamics, stable chromosome positioning, and the establishment of proper spindle size. We propose that without non-kMTs, metaphase meiotic spindles are similar to mammalian mitotic spindles, which balance forces to maintain metaphase spindle organization in the absence of extensive antiparallel microtubule overlap at the spindle equator or a key mitotic kinesin.
机译:染色体分离的准确性取决于双极纺锤体的组装。不同于有丝分裂纺锤体,后者的线粒体微管(kMTs)和非线粒体微管(non-kMTs)大致相等,脊椎动物减数分裂纺锤体主要由非kMTs组成,其中很大一部分在纺锤体上形成反平行的“桶状”阵列赤道。尽管需要kMT来驱动染色体分离,但非kMT的贡献更加神秘。在这里,我们表明增加Op18 / stathmin的浓度,可以直接消耗在非洲爪蟾卵提取物中组装的脊椎动物减数分裂纺锤体中的非kMTs,而Op18 / stathmin是染色体介导的微管形成途径的一个组成部分,直接控制微管的动态变化。在这些条件下,kMT和与主轴极点相关的非kMT阵列会保留在较小的主轴中。在过量的Op18中,姐妹kinetochores之间的距离(着重于着丝粒的方向)保持不变,即使kMT的磁极通量以约30%的速度降低,并且染色体的振荡也比对照中期纺锤体多。值得注意的是,在过量的Op18存在下,不需要kinesin-5(一种保守的运动蛋白,可以将微管推开,并且是双极减数分裂纺锤体的组装和维护所必需的)。我们的数据表明,减数分裂纺锤体中的非kMTs有助于正常的kMT动态,稳定的染色体定位以及合适的纺锤体大小的建立。我们建议,如果没有非kMTs,中期减数分裂纺锤体类似于哺乳动物的有丝分裂纺锤体,在纺锤体赤道或关键的有丝分裂驱动蛋白没有广泛的反平行微管重叠的情况下,平衡力可以维持中期纺锤体的组织。

著录项

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  • 作者单位

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York, NY 10065;

    Laboratory for Computational Cell Biology, Scripps Research Institute, La Jolla, CA 92037 Lane Center for Computational Biology and Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213;

    Laboratory for Computational Cell Biology, Scripps Research Institute, La Jolla, CA 92037;

    Laboratory for Computational Cell Biology, Scripps Research Institute, La Jolla, CA 92037;

    Laboratory of Chemistry and Cell Biology, Rockefeller University, New York, NY 10065;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    stathmin; bipolarity; flux; kinesin-5;

    机译:促炎药双极性通量驱动蛋白5;

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