The Role of EPAC- a novel Target for cAMP in the Acrosomal Exocytosis

BRANHAM MT; LOPEZ C; DE LA IGLESIA P; MAYORGA LS; TOMES C

San Carlos de Bariloche, Argentina

Congreso; Bariloche Protein Symposium; 2003

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular & Sociedad Argentina de Biofísica

Cyclic adenosine 3´, 5´-monophosphate (cAMP) is produced by adenylyl cyclase in response to a variety of extracellular stimuli. cAMP regulates a wide range of biological processes, which include cell division, growth, differentiation, and secretion. Most of these processes were thought to be mediated by cAMP-dependent protein kinase A (PKA). It has recently been proposed that cAMP also directly activates Epac, a guanine nucleotide exchange factor for the small GTPases Rap1and Rap2. The acrosome reaction (AR) is a specialized type of regulated exocytosis leading to a massive fusion between the outer acrosomal membrane and the plasma membrane of sperm cells. The induction of the AR by cAMP has been proposed to be mediated by PKA. Here we report an alternative pathway for cAMP-AR involving Epac. In a SLO permeabilized human sperm model, the Epac specific cAMP-analogue 8-CPT-2Me-cAMP triggers the AR. As is the case with calcium-dependent exocytosis, 8-CPT-2Me-cAMP induced AR is sensitive to anti-aSNAP, anti-NSF and anti- Rab3A antibodies, to intraacrosomal calcium chelators, and botulinum toxins. Our results indicate a role for Epac in mediating the AR.