Unité Mixte de Recherche 7622, Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, 75005 Paris, France.
J Cell Biol. 2010 Dec 27;191(7):1251-60. doi: 10.1083/jcb.201005065. Epub 2010 Dec 20.
In contrast to somatic cells, formation of acentriolar meiotic spindles relies on the organization of microtubules (MTs) and MT-organizing centers (MTOCs) into a stable bipolar structure. The underlying mechanisms are still unknown. We show that this process is impaired in hepatoma up-regulated protein (Hurp) knockout mice, which are viable but female sterile, showing defective oocyte divisions. HURP accumulates on interpolar MTs in the vicinity of chromosomes via Kinesin-5 activity. By promoting MT stability in the spindle central domain, HURP allows efficient MTOC sorting into distinct poles, providing bipolarity establishment and maintenance. Our results support a new model for meiotic spindle assembly in which HURP ensures assembly of a central MT array, which serves as a scaffold for the genesis of a robust bipolar structure supporting efficient chromosome congression. Furthermore, HURP is also required for the clustering of extra centrosomes before division, arguing for a shared molecular requirement of MTOC sorting in mammalian meiosis and cancer cell division.
与体细胞相反，无中心体减数分裂纺锤体的形成依赖于微管（MTs）和 MT 组织中心（MTOCs）形成稳定的双极结构。其潜在机制尚不清楚。我们发现，该过程在肝癌上调蛋白（Hurp）敲除小鼠中受损，这些小鼠具有活力但雌性不育，表现出卵母细胞分裂缺陷。HURP 通过驱动蛋白-5 （Kinesin-5）活性在染色体附近的两极间 MT 上积累。通过促进纺锤体中央域的 MT 稳定性，HURP 允许有效的 MTOC 分拣到不同的极，从而建立和维持双极。我们的结果支持了一种新的减数分裂纺锤体组装模型，其中 HURP 确保了中央 MT 阵列的组装，该阵列作为生成强大双极结构的支架，支持高效的染色体向心聚集。此外，HURP 对于分裂前额外中心体的聚类也是必需的，这表明哺乳动物减数分裂和癌细胞分裂中 MTOC 分拣具有共同的分子需求。
