Phosphoinositides and their products in the mammalian sperm acrosome reaction

At fertilization, the spermatozoon exocytoses its acrosomal granule in a Ca2(+)-dependent process known as the acrosome reaction. In mammalian spermatozoa, possibly because the acrosome is large and membrane fusion takes place between the outer acrosomal membrane and the overlying plasma membrane extensively over the anterior of the sperm head, the exocytotic process is slow and therefore amenable to biochemical dissection. By prelabelling sperm phospholipids with 32P and inducing the acrosome reaction with Ca2+ and the ionophore A23187, we have been able to show that membrane fusion occurs as the result of a sequence of events following Ca2+ entry; Ca2+ is required for at least 3 of these events. The process is initiated by a large-scale breakdown of polyphosphoinositides that is catalysed by a Ca2(+)-dependent phospholipase C. Of the resultant products, diacylglycerol is the essential one. Although its precise role remains to be established, this compound appears to stimulate a later process; it does not seem to act directly as a fusogen, nor does it act through a metabolite. However, it does not act through protein kinase C. At present we believe that diacylglycerol may simultaneously activate phospholipase A2 and inhibit lysophosphatide acyltransferase, to cause a large-scale build-up of fusogenic lysophospholipids in the acrosomal region; Ca2+ may bring about membrane fusion when the levels of these lipids have risen above a necessary threshold.