Sperm PLCζ: From structure to Ca2+ oscillations, egg activation and therapeutic potential

Significant evidence now supports the assertion that cytosolic calcium oscillations during fertilization in mammalian eggs are mediated by a testis-specific phospholipase C (PLC), termed PLC-zeta (PLC zeta) that is released into the egg following gamete fusion. Herein, we describe the current paradigm of PLC zeta in this fundamental biological process, summarizing recent important advances in our knowledge of the biochemical and physiological properties of this enzyme. We describe the data suggesting that PLC zeta has distinct features amongst PLCs enabling the hydrolysis of its substrate, phosphatidylinositol 4,5-bisphosphate (PIP2) at low Ca2+ levels. PLC zeta appears to be unique in its ability to target PIP2 that is present on intracellular vesicles. We also discuss evidence that PLC zeta may be a significant factor in human fertility with potential therapeutic capacity. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.