Protein acetylation protects sperm from spontaneous acrosome reaction

In order to penetrate the egg, spermatozoa must undergo the acrosome reaction in close proximity to the egg. This process can take place only after a series of biochemical changes in the sperm, collectively termed capacitation, occur in the female reproductive tract. Sperm cells can undergo spontaneous-acrosome reaction(sAR) before reaching the vicinity of the egg, preventing successful fertilization. Several mechanisms were shown to protect sperm from undergoing sAR, and all of them are involved in proper capacitation. Here, we describe the involvement of protein acetylation in the mechanism that protects bovine spermatozoa from sAR. Incubation of bovine sperm under non-capacitation conditions revealed a strong increase in sAR that was significantly reduced in the presence of deacetylase inhibitors. Protein kinase A (PKA) is an essential key enzyme in sperm capacitation, and its inhibition results in high sAR. The reduction in sAR by hyperacetylation was independent of PKA activity. We previously demonstrated that calmodulin-kinase II (CaMKII) activity protects sperm from sAR, and here we show that its activity is essential for reduction in sAR by hyperacetylation. We further show that the 'exchange protein directly activated by Camp' (EPAC) mediates both protein lysine acetylation and the reduced rate of sAR caused by hyperacetylation. In conclusion, these results suggest a PKA-independent and EPAC-CaMKII dependent hyperacetylation mechanism that protects sperm from sAR.