Background: How sperm sterol removal enables acrosome exocytosis (AE) is unclear; phospholipase B (PLB) is enriched in sperm membrane rafts. Results: Sterol removal leads to proteolytic activation of PLB, stimulating the initiation of changes leading to AE. Conclusion: PLB activation plays an important role in fertilization. Significance: We identify a mechanism for how sterol removal enables AE, consistent with new, zona pellucida-independent models for membrane fusion.

It is intuitive that fertilization—the start of life—involves communication between a sperm cell and an egg. It has been known that to become able to fertilize an egg, a sperm must first communicate with stimuli in the female tract. For example, sterol removal from the plasma membrane is required for sperm to undergo membrane fusion during acrosome exocytosis (AE). However, how membrane lipid changes were transduced into initiation of AE remained unclear. Recently, we found that sperm phospholipase B (PLB) is activated in response to sterol removal and released into the extracellular fluid by proteolytic cleavage. The resultant active PLB fragment can stimulate initiation of AE without other physiological stimulation. These results provide a possible mechanism for how AE is triggered, a critical question given recent data from others that show that AE is induced prior to contact with the egg’s extracellular covering, the zona pellucida.