Madgwick Suzanne, Hansen David V, Levasseur Mark, Jackson Peter K, Jones Keith T
Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle NE2 4HH, England, UK.
J Cell Biol. 2006 Sep 11;174(6):791-801. doi: 10.1083/jcb.200604140.
During interkinesis, a metaphase II (MetII) spindle is built immediately after the completion of meiosis I. Oocytes then remain MetII arrested until fertilization. In mouse, we find that early mitotic inhibitor 2 (Emi2), which is an anaphase-promoting complex inhibitor, is involved in both the establishment and the maintenance of MetII arrest. In MetII oocytes, Emi2 needs to be degraded for oocytes to exit meiosis, and such degradation, as visualized by fluorescent protein tagging, occurred tens of minutes ahead of cyclin B1. Emi2 antisense morpholino knockdown during oocyte maturation did not affect polar body (PB) extrusion. However, in interkinesis the central spindle microtubules from meiosis I persisted for a short time, and a MetII spindle failed to assemble. The chromatin in the oocyte quickly decondensed and a nucleus formed. All of these effects were caused by the essential role of Emi2 in stabilizing cyclin B1 after the first PB extrusion because in Emi2 knockdown oocytes a MetII spindle was recovered by Emi2 rescue or by expression of nondegradable cyclin B1 after meiosis I.
在减数分裂间期,减数第一次分裂完成后立即构建中期II(MetII)纺锤体。卵母细胞随后保持在MetII期停滞状态,直至受精。在小鼠中,我们发现早期有丝分裂抑制剂2(Emi2),它是一种后期促进复合体抑制剂,参与了MetII期停滞的建立和维持。在MetII期卵母细胞中,Emi2需要降解,卵母细胞才能退出减数分裂,并且通过荧光蛋白标记观察到,这种降解发生在细胞周期蛋白B1之前几十分钟。卵母细胞成熟过程中Emi2反义吗啉代寡核苷酸敲低不影响极体(PB)排出。然而,在减数分裂间期,来自减数第一次分裂的中央纺锤体微管会短暂持续存在,并且MetII纺锤体无法组装。卵母细胞中的染色质迅速解聚并形成一个细胞核。所有这些效应都是由Emi2在第一次PB排出后稳定细胞周期蛋白B1的关键作用引起的,因为在Emi2敲低的卵母细胞中,减数第一次分裂后通过Emi2拯救或通过表达不可降解的细胞周期蛋白B1可以恢复MetII纺锤体。