MAYORGA Luis Segundo
congresos y reuniones científicas
VPS4 is necessary for the acrosome deformation during acrosomal exocitosis in human sperm
POCOGNONI CA; BELMONTE SA; MAYORGA, L.S.
Congreso; 48º SAIB; 2012
The acrosome reaction of human spermatozoa is a complex, calcium-dependent regulated exocytosis. Fusion between the outer acrosomal membrane and the cell membrane causes the release of the acrosomal contents. Preventing the release of calcium from the acrosome, the exocytic process can be arrested at a stage where SNARE proteins are assembled in loose trans complexes. Transmission electron micrographs at this stage showed that the acrosomes were profusely swollen, with deep invaginations of the outer acrosomal membrane. These membrane deformations are part of the mechanism of vesiculation. Invagination of the acrosomal membrane is topologically equivalent to the formation of multivesicular bodies in endosomes, a process that depends on the assembly of the ESCRT complexes. We are exploring the possibility that the same mechanism is involved in acrosomal exocytosis. A dominant-negative mutant of VPS4, the ATPase responsible for the disassembly of the membrane attached ESCRT proteins inhibited acrosomal exocytosis of permeabilized human spermatozoa. Moreover, an anti-VPS4 antibody was also inhibitory. TEM images show abnormal bending of the acrosomal membrane when sperm were stimulated in the presence of the dominant negative VPS4. These observations suggest that the deformation of the acrosomal membrane necessary for acrosomal exocytosis are shaped by an ESCRT-dependent mechanism