PKA: the importance of being in the right place at the right time

XINRAN XU; CAROLINA BARO GRAF; CINTIA STIVAL; MARIANO G BUFFONE; MARIA G GERVASI; PABLO E VISCONTI; DARIO KRAPF; CARLA RITAGLIATI; GUILLERMINA M LUQUE; DIEGO KRAPF

Plymouth

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

Capacitation is the process that renders mammalian sperm able to fertilize an oocyte. Protein Kinase A (PKA), known to be a key player during this process, is stimulated early during capacitation. This activation is majorly guided by a rapid increase of intracellular cAMP, being this mechanism the most studied way of PKA regulation. However, current evidence supports the hypothesis that proper subcellular localization of the enzyme is also crucial for its regulation, either positioning the kinase in close contact with its substrates and regulators or, alternatively, drawing it away from them. The interaction of PKA with different anchoring proteins (AKAPs) is what determines its position within the cell.Here, we address the role of PKA localization through the usage of the anchoring inhibitor st-HT31, to study this type of PKA regulation, both in capacitation and during acrosome reaction (AR) in mouse sperm.Delocalization of PKA prevented sperm to undergo normal capacitation, resulting in an impairment of in vitro fertilization. Surprisingly, when PKA anchoring was inhibited in normally capacitated sperm, acrosome reaction (AR) was induced through a calcium-dependent mechanism. Worth noticing, even though the biological activity of PKA was affected by st-HT31, the in vitro activity of the kinase was not weaken.