Species diversity in the structure of zonadhesin, a sperm-specific membrane protein containing multiple cell adhesion molecule-like domains.

A hallmark of gamete interactions at fertilization is relative or absolute species specificity. A pig sperm protein that binds to the extracellular matrix of the egg in a species-specific manner was recently identified and named zonadhesin (Hardy, D. M., and Garbers, D. L. (1995) J. Biol. Chem. 270, 26025-26028). We have now cloned a cDNA for mouse zonadhesin (16.4 kb), and it demonstrates a large species variation in the numbers and arrangements of domains. Expression of mouse zonadhesin mRNA is evident only within the testis, and the protein is found exclusively on the apical region of the sperm head. There are 20 partial D-domains, found as tandem repeats, inserted between two of the four full D-domains and an additional partial D-domain. These domains are homologous to the D-domains of von Willebrand factor and alpha-tectorin. A region at the N terminus of the mouse cDNA contains three tandem repeats homologous to MAM domains. These are domains comprised of about 160 amino acids that are present in transmembrane proteins such as the meprins and receptor protein-tyrosine phosphatases, where they appear to function in cell/cell interactions. Additionally, mouse zonadhesin contains a mucin-like domain and a domain homologous to epidermal growth factor (EGF). A putative single transmembrane segment separates a short carboxyl tail from the extracellular region. The existence of MAM, mucin, D-, and EGF domains suggest that mouse zonadhesin functions in multiple cell adhesion processes, where binding to the extracellular matrix of the egg is but one of the functions of this sperm-specific membrane protein.