A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes

被引:127
作者
Clift, Dean [1 ]
Schuh, Melina [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
基金
欧洲研究理事会;
关键词
SMALL-MOLECULE INHIBITOR; MEIOTIC SPINDLE; CENTROSOME SEPARATION; GAMMA-TUBULIN; PROTEIN; MICROTUBULE; DYNAMICS; 1ST; REORGANIZATION; ORGANIZATION;
D O I
10.1038/ncomms8217
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Assembly of a bipolar microtubule spindle is essential for accurate chromosome segregation. In somatic cells, spindle bipolarity is determined by the presence of exactly two centrosomes. Remarkably, mammalian oocytes do not contain canonical centrosomes. This study reveals that mouse oocytes assemble a bipolar spindle by fragmenting multiple acentriolar microtubule-organizing centres (MTOCs) into a high number of small MTOCs to be able to then regroup and merge them into two equal spindle poles. We show that MTOCs are fragmented in a three-step process. First, PLK1 triggers a decondensation of the MTOC structure. Second, BicD2-anchored dynein stretches the MTOCs into fragmented ribbons along the nuclear envelope. Third, KIF11 further fragments the MTOCs following nuclear envelope breakdown so that they can be evenly distributed towards the two spindle poles. Failure to fragment MTOCs leads to defects in spindle assembly, which delay chromosome individualization and congression, putting the oocyte at risk of aneuploidy.
引用
收藏
页数:12
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