Role of Rab3il in human sperm acrosomal exocytosis

QUEVEDO MF; BUSTOS MA; TOMES CN

Rosario

Congreso; Reunión Anual Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB); 2014

SAIB

Acrosome reaction (AR) is a type of regulated exocytosis that leads to the release of the acrosome granule content. Rab3 and Rab27 constitute the two main Rabs implicated in regulated exocytosis. They localize to vesicles and secretory granules and control their recruitment, tethering, and/or docking to the plasma membrane. We have shown that, like Rab3A, Rab27 is required for exocytosis in human sperm. Both Rabs exchange GDP for GTP in response to exocytosis initiators. We were able to show that Rab3A?GTP and Rab27?GTP localize to the acrosomal region of the sperm head and active Rab27 increases the exchange of GDP for GTP on Rab3A. The molecular mechanism for this activation appears to be through a Rab?GEF cascade. A novel protein designated GRAB (guanine nucleotide exchange factor for Rab3A, also called Rab3IL) displays GEF activity for Rab3A. In this work, we present direct evidence about the localization of Rab3IL in the acrosomal region of human sperm. We also report that Rab3IL participates in an early stage during membrane fusion. And that an anti?Rab3IL antibody impairs exchange of GDP for GTP on Rab3A but not on Rab27. Finally, we demonstrate that Rab3IL interacts with Rab27?GTP bound form. Together, these results confirm the hypothesis suggested about a possible Rab?GEF cascade in human sperm and postulate Rab3IL as the possible GEF.