INVESTIGADORES
MAYORGA Luis Segundo
artículos
Título:
RIM, Munc13, and Rab3A interplay in acrosomal exocytosis
Autor/es:
BELLO, OD; ZANETTI, MN; MAYORGA, LS; MICHAUT, M.A.
Revista:
EXPERIMENTAL CELL RESEARCH
Editorial:
ELSEVIER INC
Referencias:
Lugar: Amsterdam ; Año: 2012 vol. 318 p. 478 - 488
ISSN:
0014-4827
Resumen:
Exocytosis is a highly regulated, multistage process consisting of multiple functionally definable
stages, including recruitment, targeting, tethering, priming, and docking of secretory vesicles
with the plasma membrane, followed by calcium-triggered membrane fusion. The acrosome reaction
of spermatozoa is a complex, calcium-dependent regulated exocytosis. Fusion at multiple sites
between the outer acrosomal membrane and the cell membrane causes the release of the acrosomal
contents and the loss of the membranes surrounding the acrosome. Not much is known about
the molecules that mediate membrane docking in this particular fusion model. In neurons, the formation
of the ternary RIM/Munc13/Rab3A complex has been suggested as a critical component of
synaptic vesicles docking. Previously, we demonstrated that Rab3A localizes to the acrosomal region
in human sperm, stimulates acrosomal exocytosis, and participates in an early stage during
membrane fusion. Here, we report that RIM and Munc13 are also present in human sperm and
localize to the acrosomal region. Like Rab3A, RIM and Munc13 participate in a prefusion step before
the efflux of intra-acrosomal calcium. By means of a functional assay using antibodies and recombinant
proteins, we show that RIM, Munc13 and Rab3A interplay during acrosomal exocytosis.
Finally, we report by electron transmission microscopy that sequestering RIM and Rab3A alters
the docking of the acrosomal membrane to the plasma membrane during calcium-activated acrosomal
exocytosis. Our results suggest that the RIM/Munc13/Rab3 A complex participates in acrosomal
exocytosis and that RIM and Rab3A have central roles in membrane docking.