Lysine acetylation modulates mouse sperm capacitation

Carla Ritagliati,Cintia Stival,Guillermina M Luque,Carolina Baro Graf,Dario Krapf,Mariano G Buffone

doi:10.1038/s41598-018-31557-5

Abstract

Mammalian sperm are unable to fertilize the egg immediately after ejaculation. To gain fertilization competence, they need to undergo a series of modifications inside the female reproductive tract, known as capacitation. Capacitation involves several molecular events such as phosphorylation cascades, hyperpolarization of the plasma membrane and intracellular Ca2+ changes, which prepare the sperm to develop two essential features for fertilization competence: hyperactivation and acrosome reaction. Since sperm cells lack new protein biosynthesis, post-translational modification of existing proteins plays a crucial role to obtain full functionality. Here, we show the presence of acetylated proteins in murine sperm, which increase during capacitation. Pharmacological hyperacetylation of lysine residues in non-capacitated sperm induces activation of PKA, hyperpolarization of the sperm plasma membrane, CatSper opening and Ca2+ influx, all capacitation-associated molecular events. Furthermore, hyperacetylation of non-capacitated sperm promotes hyperactivation and prepares the sperm to undergo acrosome reaction. Together, these results indicate that acetylation could be involved in the acquisition of fertilization competence of mammalian sperm.

Highlights

After ejaculation, mammalian sperm need to undergo a series of biochemical and physiological modifications inside the female reproductive tract in order to gain fertilization competence[1,2]
This result is in agreement with acetylproteome studies of human sperm[17,18], where an increase in acetylated sites of proteins important for sperm-specific functions is observed when incubated under capacitating conditions
Since some deacetylases have already been identified in human sperm[17,20], they were used as a control as well as Chinese hamster ovary (CHO) cells

Summary

Introduction

Mammalian sperm need to undergo a series of biochemical and physiological modifications inside the female reproductive tract in order to gain fertilization competence[1,2] These changes, collectively known as capacitation, prepare the sperm to develop two main features that are essential for fertilization: hyperactivated flagellar motility and the ability to undergo a secretory event known as acrosomal exocytosis. Lysine acetylation is a reversible and highly regulated PTM that is known to play a key role in modulating several cellular processes. Hyperpolarization of the plasma membrane and increased intracellular Ca2+ concentration ([Ca2+]i) through CatSper opening were observed These molecular events are all associated with the capacitated sperm state, and took place even in the absence of HCO3− and BSA. In correlation with these results, sperm aquired both hyperactivated motility and acrosomal responsiveness, pointing towards the importance of lysine acetylation in sperm physiology

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Conclusion