Lane Simon I R, Jones Keith T
Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
J Cell Biol. 2017 Dec 4;216(12):3949-3957. doi: 10.1083/jcb.201606134. Epub 2017 Oct 4.
The spindle assembly checkpoint (SAC) prevents chromosome missegregation by coupling anaphase onset with correct chromosome attachment and tension to microtubules. It does this by generating a diffusible signal from free kinetochores into the cytoplasm, inhibiting the anaphase-promoting complex (APC). The volume in which this signal remains effective is unknown. This raises the possibility that cell volume may be the reason the SAC is weak, and chromosome segregation error-prone, in mammalian oocytes. Here, by a process of serial bisection, we analyzed the influence of oocyte volume on the ability of the SAC to inhibit bivalent segregation in meiosis I. We were able to generate oocytes with cytoplasmic volumes reduced by 86% and observed changes in APC activity consistent with increased SAC control. However, bivalent biorientation remained uncoupled from APC activity, leading to error-prone chromosome segregation. We conclude that volume is one factor contributing to SAC weakness in oocytes. However, additional factors likely uncouple chromosome biorientation with APC activity.
纺锤体组装检验点（SAC）通过将后期开始与染色体正确附着以及与微管的张力相耦合来防止染色体错分离。它通过从游离的动粒向细胞质产生一种可扩散的信号来实现这一点，从而抑制后期促进复合物（APC）。该信号保持有效作用的体积尚不清楚。这就增加了一种可能性，即细胞体积可能是哺乳动物卵母细胞中SAC较弱且染色体分离容易出错的原因。在此，通过连续二等分的过程，我们分析了卵母细胞体积对SAC在减数分裂I中抑制二价体分离能力的影响。我们能够产生细胞质体积减少86%的卵母细胞，并观察到与SAC控制增强相一致的APC活性变化。然而，二价体双定向仍与APC活性解偶联，导致染色体分离容易出错。我们得出结论，体积是导致卵母细胞中SAC功能减弱的一个因素。然而，其他因素可能使染色体双定向与APC活性解偶联。
