Miyazaki Shunichi, Ito Masahiko
Department of Physiology, Tokyo Women's Medical University School of Medicine, Japan.
J Pharmacol Sci. 2006;100(5):545-52. doi: 10.1254/jphs.cpj06003x.
A dramatic increase in intracellular Ca(2+) concentration (Ca(2+)) occurs in eggs at fertilization common to all animal species examined to date, and this serves as a pivotal signal for egg activation characterized by resumption of meiotic cell division and formation of the pronuclei. In mammalian eggs, repetitive Ca(2+) rises (Ca(2+) oscillations) each of which accompanies a propagating wave across the egg occur due to release of Ca(2+) from the endoplasmic reticulum mainly through type 1 inositol 1,4,5-trisphosphate (IP(3)) receptor. Ca(2+) oscillations are induced by a cytosolic sperm factor driven into the egg cytoplasm upon sperm-egg fusion. A current strong candidate of the sperm factor is a novel sperm-specific isozyme of phospholipase C (IP(3)-producing enzyme), PLCzeta. Recent extensive research has reveled characteristics of PLCzeta such as the Ca(2+) oscillation-inducing activity after injection of PLCzeta-encoding RNA or recombinant PLCzeta into mouse eggs, extremely high Ca(2+)-sensitivity of the enzymatic activity in vitro, and nuclear translocation ability possibly related to cell-cycle-dependent regulation of Ca(2+) oscillations. Ca(2+) rises cause successive activation of calmodulin-dependent kinase II and E3 ubiquitin ligase, lead to proteolysis of ubiquitinated cyclin B1 and inactivation of metaphase-promoting factor (Cdk1/cyclin B1 complex), and result in the release of eggs from meiotic arrest.
在迄今为止所有已检测的动物物种的卵子受精过程中，细胞内钙离子浓度（[Ca(2+)]i）都会急剧增加，这是卵子激活的关键信号，其特征是减数分裂细胞分裂的恢复和原核的形成。在哺乳动物卵子中，由于内质网中钙离子主要通过1型肌醇1,4,5-三磷酸（IP(3)）受体释放，会出现重复性的[Ca(2+)]i升高（钙离子振荡），每次升高都伴随着一个跨卵子传播的波。钙离子振荡是由精子与卵子融合时进入卵细胞质的一种胞质精子因子诱导的。目前，精子因子的一个强有力候选者是一种新型的精子特异性磷脂酶C同工酶（产生IP(3)的酶），即磷脂酶Cζ。最近的广泛研究揭示了磷脂酶Cζ的一些特性，如将编码磷脂酶Cζ的RNA或重组磷脂酶Cζ注射到小鼠卵子后诱导钙离子振荡的活性、体外酶活性极高的钙离子敏感性以及可能与钙离子振荡的细胞周期依赖性调节相关的核转位能力。[Ca(2+)]i升高会导致钙调蛋白依赖性激酶II和E3泛素连接酶的相继激活，导致泛素化细胞周期蛋白B1的蛋白水解和中期促进因子（Cdk1/细胞周期蛋白B1复合物）的失活，并导致卵子从减数分裂阻滞中释放出来。
