Rajesh K. Naz

Division of Research, Department of Obstetrics and Gynecology, Medical College of Ohio, Toledo, Ohio, USA

Received 07/23/96; Accepted 07/30/96; On-line 08/15/96

The sperm proteins that bind to 55 kD ZP3, have molecular weights of 95 kD, 63 kD, 51 kD and 14-18 kD. Three of these, the 95 kD, 51 kD and 14-18 kD proteins, have phosphotyrosine residues and involve the o-phospho-L-tyrosine epitope in sperm-ZP interaction. The 51 kD protein (FA-1 antigen) also has autophosphorylating activity. Interestingly, the 55 kD ZP3 also demonstrates autophosphorylating activity in the in vitro kinase (14). At least in the in vitro system the forces involved in the sperm-ZP interaction are mainly of hydrophobic and ionic in nature. Many of these sperm proteins that participate in binding are also involved in capacitation/acrosome reaction.

Proteins with similar molecular weights have been isolated and characterized from sperm/testes in various mammalian species. The 95 ± 3 kD-proteins are involved in sperm capacitation, acrosome reaction and ZP binding in mouse (19-21) and man (18,22,23). A 63 ± 2 kD-protein has been characterized from rabbit testes (24), human sperm (25) and guinea pig testes (26), and the 51 kD protein is indeed FA-1 antigen (14). The 14-18 kD-antigens seem to correspond to proteins designated as RSA antigens (27). cDNAs encoding for some of these antigens have been cloned and sequenced. However, there is minimal sequence homology among these antigens and no common epitope has been delineated that is involved in sperm-ZP interaction/binding (28).

A vital role of protein tyrosine phosphorylation and tyrosine receptor kinases in sperm capacitation, acrosome reaction and sperm-ZP binding in humans is indicated. Since the tyrosine phosphorylation is the primary, even exclusive, indication of a signal transduction pathway, it appears that a signal transduction pathway is involved in sperm capacitation, acrosome reaction and ZP binding. However, the exact mechanism/cascade involved in signal transduction requires further study. Modulation of phosphorylation of all the proteins by a ligand (Talpha1)/antibody (anti-FA-1 mab) specifically directed against a single membrane protein (FA-1 antigen), suggests a cross-talk among these molecules. The ligand/molecule(s) that triggers the tyrosine phosphorylation, leading to capacitation and acrosome reaction is not yet identified. However, various cytokines/growth factors are present in seminal plasma (9, 29-37) and genital tract secretions of women (38,39). These proteins can potentially trigger the tyrosine phosphorylation. Presence of functional receptors (e.g.EGF receptor) for some of these ligands on human sperm membrane has been demonstrated (40). Figure 1 and Figure 2 are heuristic models constructed based on these findings.