PLCζ and the initiation of Ca(2+) oscillations in fertilizing mammalian eggs

Abstract

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.