Rabs in sperm exocytosis

BUSTOS MA; RODRIGUEZ AYALA JF; BRANHAM MT; TOMES CN

Los Cocos, Córdoba, Argentina

Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine, SISTAM 2010; 2010

SISTAM

Rab3 and Rab27 dock secretory vesicles to the plasma membrane during exocytosis. Rab3 binds GTP and associates with vesicles; it later detaches upon GTP hydrolysis. Rab27 activation and targeting differ from those of Rab3. Exocytosis of the secretory granule in sperm (the AR) is essential for fertilization; it relies on the same fusion machinery described in all cells plus cyclic AMP and Epac upstream the Rabs described above. Active Rab3A has a positive early role during the AR in human sperm. These cells contain an activity that exchanges GDP for GTP on Rab3A in response to AR triggers; the latter also enhance association of Rab3A with membranes. Surprisingly, recombinant Rab3A added at a late stage halts exocytosis if loaded with GTP-γ-S but not with GTP, indicating that hydrolysis is necessary to bring exocytosis to completion. The exocytosis block is relieved by wild type α-SNAP but not by an inactive mutant, pointing to an unsuspected link between Rab3 and SNARE complex dissociation. Rab27 localizes to the acrosomal region in human sperm and it associates with membranes in both resting and stimulated cells. Rab27 exhibits an early role during exocytosis: is required for the docking of the acrosome to the plasma membrane and, surprinsingly, for SNARE complex dissociation.