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驱动蛋白-13 KLP-7对异位微管组装的抑制作用可防止卵母细胞中的染色体分离和胞质分裂缺陷。

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

作者信息

Gigant Emmanuelle, Stefanutti Marine, Laband Kimberley, Gluszek-Kustusz Agata, Edwards Frances, Lacroix Benjamin, Maton Gilliane, Canman Julie C, Welburn Julie P I, Dumont Julien

机构信息

Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité, Paris F-75205, France.

Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK.

出版信息

Development. 2017 May 1;144(9):1674-1686. doi: 10.1242/dev.147504. Epub 2017 Mar 13.

Abstract

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 and functional assays in the 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 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.

摘要

在大多数物种中,卵母细胞缺乏中心体。因此,准确的减数分裂纺锤体组装和染色体分离(这对于防止流产或发育缺陷至关重要)是通过尚未得到充分表征的非典型机制发生的。通过在卵母细胞中进行定量和功能分析,我们提供了新的证据表明驱动蛋白-13 KLP-7促进整个细胞微管网络的不稳定。通过抵消异位微管组装和微管网络的紊乱,这种功能对于减数分裂细胞中的纺锤体组织、染色体分离和胞质分裂是严格必需的。引人注目的是,当通过实验降低中心体活性时,KLP-7的缺失或哺乳动物驱动蛋白-13蛋白MCAK(KIF2C)分别在受精卵或HeLa细胞的有丝分裂过程中导致异位微管星状体。我们的结果突出了驱动蛋白-13微管解聚酶在中心体活性有缺陷或不存在时防止异位、自发微管组装的一般功能,否则这会导致纺锤体微管紊乱和非整倍体。

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