Phospholipase Cδ4: From genome structure to physiological function

Twelve PLC isozymes have been identified in mammalian cells to date. Among them, PLCδ4 are predominantly expressed in testis and sperm. We report here the genome structure of mouse PLCδ4 gene that is approximately 28 kb in length, and composed of 17 exons. This analysis revealed that a PLCδ4 gene has four splicing isoforms, and a novel isoform, ALTIII, retained no PLC activity, because of the lack of a part of catalytic X-domain. To understand a physiological function of PLCδ4, we generated PLCδ4 gene-deficient mice. PLCδ4 gene-disrupted male mice either produced few small litters or were sterile. In vivo and in vitro fertilization studies showed that PLCδ4 has a functional role in sperm at the early step of fertilization. We also observed that the calcium transients in eggs associated with fertilization were absent or delayed when we used PLCδ4^-/- sperm. These results indicate that PLCδ4 in sperm is an essential factor for event that makes possible the initiation of calcium oscillations. Furthermore, PLCδ4^-/- sperm were unable to drive the zona pellucida-induced acrosome reaction, an exocytotic event required for fertilization. These data demonstrate that PLCδ4 functions in driving the zona pellucida-induced acrosome reaction during mammalian fertilization.