PLCζ and the initiation of Ca2+ oscillations in fertilizing mammalian eggs

Mammalian eggs undergo a prolonged series of low frequency Ca2+ oscillations at fertilization. These Ca2+ oscillations are the immediate cause of egg activation. The Ca2+ 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 (PLC zeta) is the key molecule that causes these Ca2+ 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 PLC zeta causes these oscillations and why it is so much more effective at triggering InsP3 production and Ca2+ oscillations in eggs, than other somatic isoforms of PLC. The molecular features of PLC zeta and how they relate to the pattern of Ca2+ oscillations seen at fertilization are considered. We also discuss the evidence that PLC zeta 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 PLC zeta may be targeted to these cytoplasmic vesicles by directly interacting with a specific but as yet unidentified egg PLC zeta-binding protein. (C) 2012 Elsevier Ltd. All rights reserved.