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Inhibition of ectopic microtubule assembly by the kinesin-13 KLP-7 prevents chromosome segregation and cytokinesis defects in oocytes

机译:驱动蛋白13 KLP-7抑制异位微管装配可防止卵母细胞染色体分离和胞质分裂缺陷

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摘要

In most species, oocytes lack centrosomes. Accurate meiotic spindle assembly and chromosome segregation – essential to prevent miscarriage or developmental defects – thus occur through atypical mechanisms that are not well characterized. Using quantitative in vitro and in vivo functional assays in the C. elegans oocyte, we provide novel evidence that the kinesin-13 KLP-7 promotes destabilization of the whole cellular microtubule network. By counteracting ectopic microtubule assembly and disorganization of the microtubule network, this function is strictly required for spindle organization, chromosome segregation and cytokinesis in meiotic cells. Strikingly, when centrosome activity was experimentally reduced, the absence of KLP-7 or the mammalian kinesin-13 protein MCAK (KIF2C) also resulted in ectopic microtubule asters during mitosis in C. elegans zygotes or HeLa cells, respectively. Our results highlight the general function of kinesin-13 microtubule depolymerases in preventing ectopic, spontaneous microtubule assembly when centrosome activity is defective or absent, which would otherwise lead to spindle microtubule disorganization and aneuploidy.
机译:在大多数物种中,卵母细胞缺乏中心体。准确的减数分裂纺锤体组装和染色体分离(对防止流产或发育缺陷至关重要)因此是通过特征不明确的非典型机制发生的。在秀丽隐杆线虫卵母细胞中使用定量的体外和体内功能测定,我们提供了驱动蛋白13 KLP-7促进整个细胞微管网络不稳定的新证据。通过抵消异位微管的组装和微管网络的混乱,此功能是减数分裂细胞中纺锤体组织,染色体分离和胞质分裂的严格要求。令人惊讶的是,当实验降低中心体活性时,不存在KLP-7或哺乳动物驱动蛋白13蛋白MCAK(KIF2C)也会分别在秀丽隐杆线虫合子或HeLa细胞的有丝分裂期间导致异位微管紫苑。我们的结果突出了驱动蛋白13微管解聚酶在预防或缺乏中心体活性时异位,自发性微管组装的一般功能,否则会导致纺锤体微管分解和非整倍性。

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