Participation of cysteine-rich secretory proteins (CRISP) in mammalian sperm-egg interaction

Abstract

Mammalian fertilization is a complex multi-step process mediated by different molecules present on both gametes. CRISP1 (cysteine-rich secretory protein 1) is an epididymal protein thought to participate in gamete fusion through its binding to egg-complementary sites. Structure-function studies using recombinant fragments of CRISP1 as well as synthetic peptides reveal that its egg-binding ability resides in a 12 amino acid region corresponding to an evolutionary conserved motif of the CRISP family, named Signature 2 (S2). Further experiments analyzing both the ability of other CRISP proteins to bind to the rat egg and the amino acid sequence of their S2 regions show that the amino acid sequence of the S2 is needed for CRISP1 to interact with the egg. CRISP1 appears to be involved in the first step of sperm binding to the zona pellucida, identifying a novel role for this protein in fertilization. The observation that sperm testicular CRISP2 is also able to bind to the egg surface suggests a role for this protein in gamete fusion. Subsequent experiments confirmed the participation of CRISP2 in this step of fertilization and revealed that CRISP1 and CRISP2 interact with common egg surface binding sites. Together, these results suggest a functional cooperation between CRISP1 and CRISP2 to ensure the success of fertilization. These observations contribute to a better understanding of the molecular mechanisms underlying mammalian fertilization.

Copy number changes of CRISP3 in oral squamous cell carcinoma

“…Little is known about the function of the mammalian CRISPs; however, CRISP1 and CRISP2 are known to be involved in various steps in reproduction (24). The C-terminal domain of CRISP2 has been shown to interact with calcium channels (25) and to bind a kinase present in the acrosome of mouse sperm (26).…”

The mechanism of sperm–egg interaction and the involvement of IZUMO1 in fusion

“…CRISP1 and CRISP4 are enriched in the epididymis, CRISP2 is exclusively in developing spermatids in the testes, and CRISP3 is in wider tissue distribution than the other CRISPs. 28,29 When recombinant mouse CRISP1 and CRISP2 were added to eggs, they specifically bound to the fusogenic area of mouse eggs. The antibodies against these proteins significantly inhibit the fertilization ratio.…”

Makings of the Best Spermatozoa: Molecular Determinants of High Fertility

“…These proteins have been implicated as essential contributors during sperm egg fusion. Results of experiments conducted by Cohen et al (2008) showed appearance of CRISP1 involvement in the first step of sperm binding to the zona pellucida. They also observed that sperm testicular CRISP2 is also able to bind to the egg surface which is indicative of its necessity in gamete fusion.…”