Acrosomal Matrix Proteins sp56 and AM67 and Gamete Adhesion in Mammals

Binding of free-swimming sperm to unfertilized eggs is an early step in the complex process of fertilization in mammals. Sperm bind by their head to the relatively thick, fibrillar extracellular matrix (ECM) or zona pellucida (ZP) that completely surrounds the plasma membrane of unfertilized eggs. Bound sperm penetrate the ZP, reach the space between the ZP and plasma membrane (perivitelline space), and a single sperm fuses with the egg's plasma membrane to produce a fertilized egg or zygote. In mice (Mus musculus), capacitated, acrosome-intact sperm recognize and bind to ZP3, one of three glycosylated proteins (ZP1-3) that constitute the unfertilized egg's ZP. Sperm protein-56 (sp56) or ZP3-receptor (ZP3R) was identified as a binding partner for ZP3 by photoaffinity crosslinking with ¹²⁵I-Denny-Jaffe reagent covalently linked to purified ZP3. sp56 is transiently associated with the surface of sperm heads following capacitation of sperm. AM67 is a guinea pig protein found in sperm that is orthologous with sp56 from mouse and both proteins are components of the sperm's acrosomal matrix. sp56 and AM67 are members of the C3/C4 superfamily of protein receptors (complement 4B-binding protein α) and each consists of several Sushi domains or short consensus repeats (SCR). sp56 is present during spermiogenesis in meiotic, late pachytene spermatocytes, haploid spermatids, and mature sperm, but not in other cell types. Purified native sp56 and recombinant sp56 bind to the ZP of unfertilized eggs and inhibit fertilization in vitro. On the other hand, targeted deletion of the gene encoding sp56 in males apparently has no effect on sperm binding to unfertilized eggs or on male fertility. The latter findings suggest that mouse sp56 may not be essential for fertilization in vivo or in vitro, perhaps as a consequence of functional redundancy. These and other aspects of sp56 and AM67 are reviewed here.