The sperm phospholipase C-ζ and Ca2+ signalling at fertilization in mammals

A series of intracellular oscillations in the free cytosolic Ca2+ concentration is responsible for activating mammalian eggs at fertilization, thus initiating embryo development. It has been proposed that the sperm causes these Ca2+ oscillations after membrane fusion by delivering a soluble protein into the egg cytoplasm. We previously identified sperm-specific phospholipase C (PLC)-zeta as a protein that can trigger the same pattern of Ca2+ oscillations in eggs seen at fertilization. PLC zeta appears to be the elusive sperm factor mediating egg activation in mammals. It has potential therapeutic use in infertility treatments to improve the rate of egg activation and early embryo development after intra-cytoplasmic sperm injection. A stable form of recombinant human PLC zeta could be a prototype for use in such in vitro fertilization (IVF) treatments. We do not yet understand exactly how PLC zeta causes inositol 1,4,5-trisphosphate (InsP(3)) production in eggs. Sperm PLC zeta is distinct among mammalian PI-specific PLCs in that it is far more potent in triggering Ca2+ oscillations in eggs than other PLCs, but it lacks a PH domain that would otherwise be considered essential for binding to the phosphatidylinositol 4,5-bisphosphate (PIP2) substrate. PLC zeta is also unusual in that it does not appear to interact with or hydrolyse plasma membrane PIP2. We consider how other regions of PLC zeta may mediate its binding to PIP2 in eggs and how interaction of PLC zeta with egg-specific factors could enable the hydrolysis of internal sources of PIP2.