Fertilization

To examine sperm binding in cells that either do or do not express alpha6, Almeida et al. utilized cultured mouse macrophages. These cells do not express alpha6 and do not bind sperm. However, when they were transfected with an alpha6 gene, sperm binding was seen (compare Fig. 5E and F). The alpha6 subunits were presumably binding with endogenous �1 subunits to produce functional alpha6�1. Together, these studies with cultured cells indicate that simultaneous expression of alpha6 and �1 is necessary for sperm binding.

Next, Almeida et al. examined the role of fertilin in alpha6�1-mediated sperm binding by using a synthetic peptide corresponding to the predicted integrin-binding portion of the disintegrin domain. As shown in Figure 6A, this peptide inhibited sperm binding to eggs, indicating that fertilin mediates sperm binding to alpha6�1. This possibility was further examined by testing the effects of this peptide on the binding of anti-alpha6 antibody to the egg surface. As shown in Figure 7, the peptide significantly reduced antibody binding to eggs, indicating that the peptide and the antibody competed for binding to the same molecule.

These data suggest that binding between disintegrins in sperm and integrins in the egg plasma membrane is responsible for gamete interaction in mammals.

The final step in fertilization is sperm/egg fusion. Although fusion is known to be facilitated by the acrosome reaction, the actual mechanism of fusion is unclear. Presumably, some change occurs on the sperm surface during the acrosome reaction to facilitate fusion. The initial site of fusion on the sperm is the equatorial segment (see your text). The antigenic properties of the equatorial segment change after the acrosome reaction. Furthermore, neutralizing antibodies against the equatorial segment of acrosome-reacted sperm block sperm/egg fusion. These results suggest that alterations to the equatorial segment facilitate sperm/egg fusion (Allen and Green, 1997).