INVESTIGADORES
BELMONTE Silvia Alejandra
artículos
Título:
Cholesterol content regulates acrosomal exocytosis by enhancing Rab3A plasma membrane association.
Autor/es:
BELMONTE, SILVIA A; LOPEZ CECILIA INÉS; ROGGERO, CARLOS M; DE BLAS, GERARDO A; TOMES, CLAUDIA N; MAYORGA, LUIS S
Revista:
DEVELOPMENTAL BIOLOGY
Editorial:
Elsevier
Referencias:
Lugar: Amsterdam; Año: 2005 vol. 285 p. 393 - 408
ISSN:
0012-1606
Resumen:
The acrosome is an exocytic granule that overlies the spermatozoan nucleus. In response to different stimuli, it undergoes calcium regulated
exocytosis. Freshly ejaculated mammalian sperm are not immediately capable of undergoing acrosome reaction. The acquisition of
this ability is called capacitation and involves a series of still not well-characterized changes in the sperm physiology. Plasma membrane
cholesterol removal is one of the sperm modifications that are associated with capacitation. However, how sterols affect acrosomal exocytosis
is unknown. Here, we show that short incubations with cyclodextrin, a cholesterol removal agent, just before stimulation promote acrosomal
exocytosis. Moreover, the effect was also observed in permeabilized cells stimulated with calcium, indicating that cholesterol plays a direct
role in the calcium-dependent exocytosis associated with acrosome reaction. Using a photo-inhibitable calcium chelator, we show that
cholesterol affects an early event of the exocytic cascade rather than the lipid bilayers mixing. Functional data indicate that one target for the
cholesterol effect is Rab3A. The sterol content does not affect the Rab3A activation?deactivation cycle but regulates its membrane
anchoring. Western blot analysis and immunoelectron microscopy confirmed that cholesterol efflux facilitates Rab3A association to sperm
plasma membrane. Our data indicate that the cholesterol efflux occurring during capacitation optimizes the conditions for the productive
assembly of the fusion machinery required for acrosome reaction.
D 2005 Published by Elsevier Inc.2005 Published by Elsevier Inc.