CONICET | Buscador de Institutos y Recursos Humanos

Mammalian sperm are unable to fertilize the egg before undergoing a series of biochemical and physiological changes in the female reproductive tract, collectively known as capacitation. Functionally, capacitation is associated with changes in the sperm motility (hyperactivation) and with their ability to undergo the acrosome reaction. At the molecular level, capacitation correlates with activation of the cAMP-PKA pathway, increase in intracellular pH and Ca2+ concentration, hyperpolarization of the plasma membrane potential, loss of cholesterol and other lipid modifications and increase in protein tyrosine phosphorylation. How these signaling pathways interact to induce hiperactivation and the acrosome reaction is not well understood. Since mature sperm are transcriptionally and translationally silent, they rely on postranslational modifications (PTM) of proteins 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. Acetylation as a broad and abundant PTM comparable with phosphorylation, however, has not been well analyzed. Recently, two groups identified 576 and 456 acetylated proteins in capacitated and non capacitated human sperm respectively, 250 were present in both conditions. In the present work, we studied the role of acetylation in capacitation of mouse and human sperm. WB analysis with anti-acetyl lysine antibodies showed lysine acetylation of lots of proteins spanning a wide mass range. Acetylation of proteins was associated with PKA activity. In addition, this PMT is necessary for hyperpolarization of the sperm plasma membrane, which is a prerequisite for acrosome reaction. These results point towards a key role of lysine acetylation in sperm capacitation.