Tsaadon Alina, Eliyahu Efrat, Shtraizent Nataly, Shalgi Ruth
Department of Cell & Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):107-14. doi: 10.1016/j.mce.2006.03.037. Epub 2006 May 9.
Embryonic development is initiated after the fertilizing spermatozoon enters the egg and triggers a series of events known as egg activation. Activation results in an increase in intracellular calcium concentration, cortical granule exocytosis (CGE), cell cycle resumption and recruitment of maternal mRNA. CGE is an evolutionary developed mechanism that causes modification of the zona pellucida to prevent penetration of additional spermatozoa, ensuring successful egg activation and embryo development. The egg CGE is a unique and convenient mammalian model for studying the different proteins participating at the membrane fusion cascade, which, unlike other secretory cells, occurs only once in the egg's lifespan. This article highlights a number of proteins, ascribed to participate in CGE and thus the block to polyspermy. CGE can be triggered either by a calcium dependent pathway, or via protein kinase C (PKC) activation that requires a very low calcium concentration. In a recent study, we suggested that the filamentous actin (F-actin) at the egg's cortex is a dynamic network. It can be maneuvered towards allowing CGE by activated actin associated proteins and/or by activated PKC and its down stream proteins, such as myristoylated alanine-rich C kinase substrate (MARCKS). MARCKS, a protein known to cross-link F-actin in other cell types, was found to be expressed and colocalized with actin in non-activated MII eggs. We further demonstrated MARCKS dissociation from actin after activation by ionomycin, a process that can lead to the breakdown of the actin network, thus allowing CGE. The more we know of the intricate process of CGE and of the proteins participating in it, the more the assisted reproductive procedures might benefit from that knowledge.
胚胎发育始于受精精子进入卵子并触发一系列称为卵子激活的事件。激活导致细胞内钙浓度增加、皮质颗粒胞吐作用（CGE）、细胞周期恢复以及母体mRNA的募集。CGE是一种进化而来的机制，可导致透明带发生改变，以防止额外精子穿透，确保卵子成功激活和胚胎发育。卵子CGE是一种独特且便捷的哺乳动物模型，用于研究参与膜融合级联反应的不同蛋白质，与其他分泌细胞不同，这种反应在卵子的生命周期中只发生一次。本文重点介绍了一些被认为参与CGE从而防止多精受精的蛋白质。CGE可由钙依赖性途径触发，或通过需要极低钙浓度的蛋白激酶C（PKC）激活来触发。在最近的一项研究中，我们提出卵子皮质处的丝状肌动蛋白（F-肌动蛋白）是一个动态网络。它可以通过激活的肌动蛋白相关蛋白和/或激活的PKC及其下游蛋白（如富含肉豆蔻酰化丙氨酸的C激酶底物（MARCKS））来调控，从而实现CGE。MARCKS是一种已知在其他细胞类型中可交联F-肌动蛋白的蛋白质，发现在未激活的MII期卵子中表达并与肌动蛋白共定位。我们进一步证明，离子霉素激活后，MARCKS与肌动蛋白解离，这一过程可导致肌动蛋白网络的解体，从而实现CGE。我们对CGE的复杂过程及其参与蛋白了解得越多，辅助生殖程序可能从这些知识中受益就越多。
