MEMBRANE FUSION DURING ACROSOMAL EXOCYTOSIS: MOLECULES AND SOMETHING ELSE

TOMES CLAUDIA NORA

Viña del Mar

Congreso; XXVIII Reunión Anual Sociedad Chilena de Reproducción y Desarrollo; 2017

Sociedad Chilena de Reproducción y Desarrollo

Secretory cells undergo regulated exocytosis to release biological compounds and to insert lipids and proteins into the plasma membrane. At the final stage of exocytosis, a fusion pore opens between the plasma and a secretory vesicle membranes; typically, when the pore dilates the vesicle releases its cargo. My lab uses the exocytosis of the acrosomal vesicle of human sperm (the acrosome reaction or AR) as model system. Each sperm contains a single, very large and electron dense granule whose contents are secreted by a regulated exocytosis at fertilization. The acrosomal membrane fuses at multiple points with the plasma membrane that overlies the anterior part of the head. Joining of pores originates hybrid plasma membrane-outer acrosomal membrane vesicles. The AR is completed when vesicles and acrosomal contents are shed. My lab is interested in unveiling the molecular mechanisms that govern the AR. In the first part of my talk I will describe two proteins that connect the small GTPases Rab27 and Rab3. In the second part, I will introduce work we have conducted with Rab3A/Rab22A chimaeric proteins: the carboxy-terminus domain of Rab3A is necessary and sufficient to promote exocytosis whereas its amino-terminus prevents calcium-triggered secretion. We have applied funcional assays, electron and confocal microscopy and biochemical approaches to show that the Rab3A-22A chimaera blocks secretion because it stabilizes open fusion pores. In other words, vesiculation is not spontaneous as it was always assumed; rather, post-fusion regulation of the pores determines their expansion and the success of the AR.