Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension
Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension
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DOI：
10.1242/dev.077040
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发表时间：
2012-06-01
期刊：
影响因子：
4.6
通讯作者：
Jones, Keith T.
中科院分区：
文献类型：
--
作者：
Lane, Simon I. R.;Yun, Yan;Jones, Keith T.
减数分裂 I 期间的同源染色体分离错误很常见，并产生非整倍体胚胎。在这里，我们通过小鼠卵母细胞的活细胞成像提供了这种对错误分离的敏感性的原因。我们的结果表明，稳定的着丝粒-微管附着在中期中期、后期前 3-4 小时形成。这与着丝粒中 Mad2 的丢失以及后期促进复合物/环体 (APC/C) 介导的细胞周期蛋白 B1 破坏的开始相一致。因此，纺锤体组装检查点（SAC）从中期中期开始不再抑制 APC/C。这个时间与所有检查的卵母细胞中有三分之一的二价国会不一致。未对齐的二价体对 Mad2 呈弱阳性，其张力低于国会二价体，并且通过活细胞成像，似乎正在建立正确的双方向。从 APC/C 变得活跃到后期开始的时间受 CDK1 活性丧失率的影响，而不是受这些不对齐的二价体的影响，这些不对齐的二价体偶尔会持续到后期，导致同源物不分离。我们的结论是，在卵母细胞中，二价着丝粒与微管的一些错误附着不会产生足够的 SAC“等待后期”信号来抑制 APC/C。
Homologous chromosome segregation errors during meiosis I are common and generate aneuploid embryos. Here, we provide a reason for this susceptibility to mis-segregation by live cell imaging of mouse oocytes. Our results show that stable kinetochore-microtubule attachments form in mid-prometaphase, 3-4 hours before anaphase. This coincided with the loss of Mad2 from kinetochores and with the start of anaphase-promoting complex/cyclosome (APC/C)-mediated cyclin B1 destruction. Therefore, the spindle assembly checkpoint (SAC) ceased to inhibit the APC/C from mid-prometaphase. This timing did not coincide with bivalent congression in one-third of all oocytes examined. Non-aligned bivalents were weakly positive for Mad2, under less tension than congressed bivalents and, by live-cell imaging, appeared to be in the process of establishing correct bi-orientation. The time from when the APC/C became active until anaphase onset was affected by the rate of loss of CDK1 activity, rather than by these non-aligned bivalents, which occasionally persisted until anaphase, resulting in homolog non-disjunction. We conclude that, in oocytes, a few erroneous attachments of bivalent kinetochores to microtubules do not generate a sufficient SAC `wait anaphase' signal to inhibit the APC/C.