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)-ζ as a protein that can trigger the same pattern of Ca²⁺ oscillations in eggs seen at fertilization. PLCζ 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 PLCζ could be a prototype for use in such in vitro fertilization (IVF) treatments. We do not yet understand exactly how PLCζ causes inositol 1,4,5-trisphosphate (InsP₃) production in eggs. Sperm PLCζ 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. PLCζ is also unusual in that it does not appear to interact with or hydrolyse plasma membrane PIP₂. We consider how other regions of PLCζ may mediate its binding to PIP₂ in eggs and how interaction of PLCζ with egg-specific factors could enable the hydrolysis of internal sources of PIP₂.