Molecular triggers of egg activation at fertilization in mammals

Abstract

In mammals, the sperm activates the development of the egg by triggering a series of oscillations in the cytosolic-free Ca2+ concentration (Ca2+i). The sperm triggers these cytosolic Ca2+i oscillations after sperm-egg membrane fusion, as well as after intracytoplasmic sperm injection (ICSI). These Ca2+i oscillations are triggered by a protein located inside the sperm. The identity of the sperm protein has been debated over many years, but all the repeatable data now suggest that it is phospholipase Czeta (PLCζ). The main downstream target of Ca2+i oscillations is calmodulin-dependent protein kinase II (CAMKII (CAMK2A)), which phosphorylates EMI2 and WEE1B to inactivate the M-phase promoting factor protein kinase activity (MPF) and this ultimately triggers meiotic resumption. A later decline in the activity of mitogen-activated protein kinase (MAPK) then leads to the completion of activation which is marked by the formation of pronuclei and entry into interphase of the first cell cycle. The early cytosolic Ca2+ increases also trigger exocytosis via a mechanism that does not involve CAMKII. We discuss some recent developments in our understanding of these triggers for egg activation within the framework of cytosolic Ca2+ signaling.