Role of actin cytoskeleton in mammalian sperm capacitation and the acrosome reaction

Abstract

In order to fertilize, the mammalian spermatozoa should reside in the female reproductive tract for several hours, during which they undergo a series of biochemical modifications collectively called capacitation. Only capacitated sperm can undergo the acrosome reaction after binding to the egg zona pellucida, a process which enables sperm to penetrate into the egg and fertilize it. Polymerization of globular (G)-actin to filamentous (F)-actin occurs during capacitation, depending on protein kinase A activation, protein tyrosine phosphorylation, and phospholipase D activation. F-actin formation is important for the translocation of phospholipase C from the cytosol to the sperm plasma membrane during capacitation. Prior to the occurrence of the acrosome reaction, the F-actin should undergo depolymerization, a necessary process which enables the outer acrosomal membrane and the overlying plasma membrane to come into close proximity and fuse. The binding of the capacitated sperm to the zona pellucida induces a fast increase in sperm intracellular calcium, activation of actin severing proteins which break down the actin fibers, and allows the acrosome reaction to take place.

Autophagy is required for ectoplasmic specialization assembly in sertoli cells

“…2,19,39,49 The cytoskeleton is a highly organized dynamic structure that plays a key role in the shaping and differentiating of spermatids. 50 Two cytoskeletal structures in the seminiferous epithelium, the Sertoli cell apical ES and the spermatid-containing acrosome-acroplaxome-manchette complex, may play cooperative roles in the shaping of the sperm head. 38,39,51 The Sertoli cell apical ES encircles and mechanically grasps the acrosome of the elongating spermatid head with a narrow layer of hexagonally packed, parallel actin bundles.…”

Role and Regulation of Sperm Gelsolin Prior to Fertilization

“…Another important process that occurs during sperm capacitation is actin polymerization; however, at the end of the capacitation, the polymers must disperse to achieve the AR (3). It has been suggested that an increase in F-actin creates a network between the plasma and the outer acrosomal membranes, and the dispersion of F-actin between the two membranes is needed to enable the AR (3)(4)(5)(6).…”

“…Phosphoinositides release gelsolin from actin filament ends, providing sites for actin assembly (14 -17). In vitro studies suggested that gelsolin is phosphorylated by pp60(c-SRC) and that this phosphorylation is enhanced by phosphoinositide 4,5-bisphosphate (PIP 2 (4,5) ) (18) and can interfere with the binding of gelsolin to the actin filaments (19). Previous work identified SRC in human spermatozoa, and it appears to be involved in regulating sperm capacitation, calcium fluxes, tyrosine phosphorylation, and the acrosome reaction (20).…”

“…It was suggested that EGFR is phosphorylated at the SRC-specific site, suggesting that SRC is active during capacitation (21,22). Additionally, EGFR-mediated signaling is known to activate phospholipase C␥ (PLC␥), to hydrolyze PIP 2 (4,5) , and to cause the subsequent release of PIP 2(4,5) -bound proteins. In vitro studies have shown that gelsolin modulates the activity of several signaling enzymes, including PLC and phospholipase D through interactions with PIP 2(4,5) (23)(24)(25)(26)(27)).…”

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study

“…In particular, two possible roles for PKC in acrosome reaction have been proposed: the first is to trigger a plasma membrane calcium channel to increase intracellular Ca 2+ (Galizzi et al, 1987;Spungin & Breitbart, 1996); the second one is to activate the phospholipase A 2 (PLA 2 ) that generates arachidonic acid (Roldan et al, 1992). Interestingly, a crosstalk between PKA and PKC during sperm capacitation was highlighted by Cohen and colleagues (Cohen et al, 2004;Breitbart et al, 2005) with a consequent rapid increase in actin polymerization which is followed by fast depolymerization, probably because of the increase in Ca 2+ levels. Therefore, spermatozoa ability to fertilize is tightly associated to a remodeling in cytoskeletal compounds.…”