Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Cell Calcium. 2013 Jan;53(1):55-62. doi: 10.1016/j.ceca.2012.11.001. Epub 2012 Dec 5.
Mammalian eggs undergo a prolonged series of low frequency Ca(2+) oscillations at fertilization. These Ca(2+) oscillations are the immediate cause of egg activation. The Ca(2+) oscillations in mouse eggs have been shown to be driven by increased InsP(3) production. Substantial evidence now indicates that a sperm-derived phospholipase C-zeta (PLCζ) is the key molecule that causes these Ca(2+) oscillations at fertilization. The fertilizing sperm is envisaged to introduce this essential molecule into the egg following gamete fusion. This review summarizes our current knowledge of how sperm PLCζ causes these oscillations and why it is so much more effective at triggering InsP(3) production and Ca(2+) oscillations in eggs, than other somatic isoforms of PLC. The molecular features of PLCζ and how they relate to the pattern of Ca(2+) oscillations seen at fertilization are considered. We also discuss the evidence that PLCζ does not hydrolyze the conventional source of PI(4,5)P(2) in the plasma membrane to make InsP(3), but instead uses a distinct pool of PI(4,5)P(2) present on intracellular vesicles. This leads us to suggest that sperm PLCζ may be targeted to these cytoplasmic vesicles by directly interacting with a specific but as yet unidentified egg PLCζ-binding protein.
哺乳动物卵子在受精时会经历一系列低频的钙离子振荡。这些钙离子振荡是卵子激活的直接原因。已经表明，小鼠卵子中的钙离子振荡是由 InsP(3)产生增加驱动的。现在有大量证据表明，精子衍生的磷脂酶 C-ζ（PLCζ）是在受精时引起这些钙离子振荡的关键分子。设想受精精子在配子融合后将这种必需分子引入卵子。这篇综述总结了我们目前对精子 PLCζ 如何引起这些振荡以及为什么它在触发卵子中 InsP(3)产生和钙离子振荡方面比其他体细胞 PLC 同工酶更有效率的认识。还考虑了 PLCζ 的分子特征以及它们与受精时观察到的钙离子振荡模式的关系。我们还讨论了证据表明 PLCζ 不会水解质膜中 PI(4,5)P(2)的常规来源来产生 InsP(3)，而是使用存在于细胞内囊泡上的独特 PI(4,5)P(2)池。这使我们推测，精子 PLCζ 可能通过直接与特定但尚未鉴定的卵子 PLCζ 结合蛋白相互作用而被靶向到这些细胞质囊泡。
