Lysine acetylation is a new regulation mechanism of human sperm capacitation

CARLA RITAGLIATI; MARIANO G BUFFONE; CINTIA STIVAL; CAROLINA BARO GRAF; DARIO KRAPF

Holderness

Conferencia; Fertilization & Activation of Development - Gordon Research Conference; 2019

Gordon Research Conferences

Mammalian sperm are unable to fertilize the egg immediately after ejaculation. To gain fertilization competence, they need to undergo a series of biochemical and physiological changes in 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 (AR). How these signaling pathways interact to induce hyperactivation and acrosomal responsiveness is not well understood. Since mature sperm are transcriptionally and translationally silent, they rely on postranslational modifications (PTM) more than any other cell type. Therefore, it is an exceptional model for the study of signaling pathways based on PTM. The importance of phosphorylation, an essential PTM in sperm physiology has been well established. On the other hand, acetylation of proteins, in spite of being as abundant and ubiquous as phosphorylation, has not been much explored in sperm. Recently, two groups identified 456 and 576 acetylated proteins in non-capacitated and capacitated human sperm respectively. Different acetylation profiles were observed in proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization, indicating that acetylation might be required for sperm capacitation and fertilization. Interestingly, both PKAc and PKARII appeared to be acetylated in Lys267 and Lys379 respectively, only in capacitated sperm. In this context, the general aim of our work was to study the role of protein acetylation in the signaling cascade responsible for the acquisition of fertilizing capacity of mammalian sperm. We recently reported that pharmacological hyperacetylation in non-capacitated mice sperm induced activation of PKA, hyperpolarization of the sperm plasma membrane, CatSper opening and Ca2+ influx, all capacitation-associated molecular events. In correlation with these results, sperm acquired both hyperactivated motility and acrosomal responsiveness, pointing towards the importance of lysine acetylation in sperm physiology. Our current work in human sperm shows that incubation in non-capacitating media with deacetylase inhibitors increased PKA substrates and Tyr phosphorylation, induced hyperpolarization of the plasma membrane at shorter times than the capacitating media, prepared the sperm for the AR and induced CatSper opening.