Sperm penetration, acrosin

The acrosome reaction is the loss of the acrosomal and plasma membranes in the acrosome region and the release of acrosin, hyaluronidase and other enzymes that disperse the cumulus complex and allow the sperm to penetrate the zona pellucida. After capacitation and the acrosome reaction, sperm penetrate the extracellular cumulus matrix and bind with zona protein 3, a heavily glycosylated protein of the zona pellucida. The first segment of the sperm to make contact with the oolemma is usually the inner acrosomal membrane, followed by the postacrosomal region. The plasma membrane of the sperm attaches to microvilli on the oolemma. Sperm-egg fusion is apparent from reduced movement of the sperm tail (Yanagimachi, 1970,1988 Takano et al.,... 

The m - and subsequent hydrolytic products of m -acrosin are not as susceptible to inhibition with these carbohydrates as is m -acrosin (53). These data provide evidence for a model for the penetration of ZP by sperm by a sequential binding, hydrolysis, and subsequent rebinding that would be necessary for sperm penetration of the ZP. 

Sperm penetrate the zona pellucida only after completion of the acrosome reaction. A similar process occurs in nonmammalian species, where sperm must penetrate the vitelline coat. In abalone this is accomplished by release of lysin, an acrosomal protein that disperses the vitelline coat by a noncatalytic mechanism (Lewis et al., 1982 Shaw et al., 1993). In contrast, the generally accepted model for mammalian sperm penetration of the zona pellucida is the acrosin hypothesis in which proteolysis of zona pellucida matrix glycoproteins by acrosin, the acrosomal serine esterase, plays a trailblazing role in the sperm penetration process (Yanag-... 

Since the 28K-proacrosin interaction required either 8 M urea or 6 M guanidine HC1 to disrupt it (10), this protein-protein interaction may act to anchor proacrosin to the acrosomal membranes or to other proacrosin molecules. While acrosin does not fit all the criteria for an intrinsic membrane protein, acrosin was associated with and extracted from preparations of sperm membrane vesicles with 1 mM HC1 and Triton X-100 (5 , Urch, unpublished observations). Salt or combinations of salt and detergent were ineffective. The interaction of acrosin with membranes, particularly sperm acrosomal membranes, is obviously important in ZP binding and penetration. 

The third criterion of the inhibition of fertilization by active site inhibitors was observed both In vitro (63) and in vivo (64) fertilization. However, this inhibition was never total, and once the sperm had tightly bound the ZP, trypsin active site inhibitors did not prevent further penetration or hydrolysis of the ZP (65). Therefore, while acrosin does not strictly follow all of the criteria for a ZP lysin, it does cause limited hydrolysis of the ZP and it is in the correct place to act in penetration of the ZP. 

Figure 3. A Model for Acrosin s Role in Zona Pellucida Binding and Penetration of Sperm. The model uses the m -acrosin form depicted in Figure 2. Acrosin is bound to the sperm plasma membrane (PM) via its hydrophobic domain and interacts with the egg zona pellucida (ZP) via its protease and carbohydrate binding domains. The ZP is composed of three glycoproteins which have unique polypeptide chains and both shared and unique oligosaccharide moieties. Symbols used - oligosaccharide...

Baba, T., Azuma, S., Kashiwabara, S., and Toyoda, Y. (1994). Sperm from mice carrying a targeted mutation of the acrosin gene can penetrate the oocyte zona pellucida and effect fertilization. J. Biol. Chem. 269 31845-31849. 

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