Department of Cardiology, University of Heidelberg, 69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):81-6. doi: 10.1073/pnas.0912658106. Epub 2009 Dec 4.
Fertilization triggers a rise in intracellular Ca(2+) concentration (Ca(2+)) in the egg that initiates a series of events known as egg activation. These events include cortical granule exocytosis that establishes a block to polyspermy, resumption of meiosis, and recruitment of maternal mRNAs into polysomes for translation. Several calcium-dependent proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), have been implicated in egg activation. However, the precise role of CaMKII in mediating specific events of egg activation and the identity of the isoform(s) present in mouse eggs have not been unequivocally established. Through targeted deletion of the gamma isoform of CaMKII, we find that CaMKIIgamma is the predominant CaMKII isoform in mouse eggs and that it is essential for egg activation. Although CaMKIIgamma(-/-) eggs exhibit a normal pattern of Ca(2+) oscillations after insemination and undergo cortical granule exocytosis, they fail to resume meiosis or to recruit maternal mRNAs. Surprisingly, we find that the recruitment of maternal mRNAs does not directly depend on CaMKII, but requires elevated Ca(2+) and metaphase II exit. We conclude that CaMKIIgamma specifically controls mouse egg activation by regulating cell cycle resumption.
受精会引发卵子内细胞钙离子浓度 (Ca(2+)) 的上升，从而引发一系列被称为卵子激活的事件。这些事件包括皮质颗粒胞吐作用，从而建立阻止多精入卵的屏障、恢复减数分裂以及将母源 mRNA 募集到多核糖体进行翻译。几种钙依赖性蛋白，包括钙/钙调蛋白依赖性蛋白激酶 II（CaMKII），已被牵连到卵子激活中。然而，CaMKII 在介导卵子激活的特定事件中的精确作用以及在小鼠卵子中存在的同工型（s）的身份尚未得到明确确立。通过靶向删除 CaMKII 的γ同工型，我们发现 CaMKIIγ是小鼠卵子中主要的 CaMKII 同工型，对于卵子激活是必不可少的。尽管 CaMKIIγ(-/-) 卵子在受精后表现出正常的钙离子振荡模式并发生皮质颗粒胞吐作用，但它们无法恢复减数分裂或募集母源 mRNA。令人惊讶的是，我们发现母源 mRNA 的募集并不直接依赖于 CaMKII，而是需要升高的 Ca(2+) 和 M 期 II 退出。我们得出结论，CaMKIIγ 通过调节细胞周期恢复来特异性控制小鼠卵子激活。
