ROLE OF CALCINEURIN DURING ACROSOMAL EXOCYTOSIS OF HUMAN SPERM

CASTILLO BENNETT, JIMENA; ROGGERO CARLOS MARCELO; MAYORGA LUIS SEGUNDO

MAR DEL PLATA

Congreso; XLIII Reunión Anual de la Soc. Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2007

Synaptotagmins (syt) are transmembrane proteins with two cytoplasmatic calcium- and phospholipids-binding domains (C2A and C2B). Synaptotagmins have been involved in exocytosis as calcium sensors. The acrosome exocytosis (AE) is a calcium regulated exocytosis essential for fertilization. We have demonstrated that syt VI is required for the AE and that Syt VI is phosphorylated in resting sperm, and its dephosphorylation after stimulation requires calcium. Calcineurin is a calcium/calmodulinactivated serine/threonine protein phosphatase whose role in exocytosis is still unclear. Our aim is to unveil whether calcineurin is involved in dephosphorylation of syt VI in human sperm. To this end, we have used a streptolysin O permeabilized sperm model. Cyclosporin A and FK 506, two calcineurin inhibitors, blocked the RA at the same early step where syt is dephosphorylated. In an in vitro phosphorylation/dephosphorylation assay calcineurin dephosphorylated syt VI C2B domain when it was activated with calcium and calmodulin. Our results indicate that calcineurin dephosphorylate syt VI during acrosomal exocytosis.