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Query: UMLS:C0155339 (Brown)
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One conclusion that may be drawn from the foregoing discussion is that examination of mammalian gamete interaction at a molecular level is underway. As yet, however, it would be premature to suggest a detailed molecular model to account fully for acrosomal exocytosis. Too many possibilities exist at present, not just for sperm but for virtually all other exocytotic systems studied. It is evident, however, that many elements of typical signal transduction pathways are present in sperm, and recent work supports the idea that such pathways may be used in AR triggering. Investigations at the cellular level provide sufficient data to formulate a sequence of gamete interactions that may apply generally to mammals. This sequence is summarized in Fig. 8.2. It is suggested that the cumulus ECM functions to restrict access of only primed (i.e., capacitated) sperm to the egg. Those sperm that undergo a spontaneous AR in the midst of the cumulus ECM are prevented from further participation in fertilization by adherence to cumulus cells. Thus, a select population of capacitated, acrosome-intact sperm arrive at the zona pellucida surface under the normal conditions of fertilization. Binding to the zona pellucida is initiated by plasma membrane receptors interacting with ZP3. This primary binding results in receptor clustering, which itself is the triggering event for acrosomal exocytosis. The signal is transmitted intracellularly via G proteins to effect fusion between the plasma and outer acrosomal membranes. As a result, proacrosin is exposed. Direct evidence for specific use of ZP2 in secondary binding has not yet been reported, but is inferred from results with mouse (Bleil and Wassarman 1986), and procine (Brown and Jones 1987; Jones et al. 1988; Topfer-Petersen and Henschen 1987, 1988) gametes. This secondary binding between ZP2 and proacrosin occurs together with pH-dependent autoactivation of proacrosin to acrosin. Limited proteolysis of the zona pellucida matrix by acrosin causes digestion and increases the affinity of freshly exposed proacrosin for the zona pellucida. This cycle continues, eventually generating the narrow penetration slit through the zona pellucida. Undoubtedly, other factors are at play here, particularly motility, and it is assumed that vigorously active ('hyperactive') sperm are the cells that participate in these events. This scheme can account for the many diverse observations made in different species if two factors, kinetics and affinity, are considered. In some species, FTU aggregation may occur spontaneously at a rate faster than in others, leading to a higher level of spontaneously acrosome-reacted sperm.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mammalian sperm interaction with extracellular matrices of the egg. 269 32

The initial stages of fertilization in vertebrates and invertebrates are thought to involve complementary recognition molecules on spermatozoa and eggs. In a previous work (C. R. Brown and R. Jones, 1987, Development) we described one such putative molecule (a protein of approximate molecular weight 53 kDa) in detergent extracts of boar spermatozoa that has affinity for glycoproteins from the zona pellucida of pig eggs. This molecule has now been identified as proacrosin, the zymogen form of the acrosomal protease acrosin, on the basis of its electrophoretic behavior, the ability of zona glycoproteins to recognize and bind to proacrosin on Western blots, and the cross-reactivity of specific antisera to the 53-kDa molecule and proacrosin. A role is proposed for this enzyme in binding the sperm head to the zona pellucida during the initial stages of sperm-egg interaction.
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PMID:Identification of a zona-binding protein from boar spermatozoa as proacrosin. 311 89