Cysteine-Rich Secretory Proteins (CRISP) and their role in mammalian fertilization

Abstract

Epididymal protein CRISP1 is a member of the CRISP (Cysteine-RIch Secretory proteins) family and is involved in sperm-egg fusion through its interaction with complementary sites on the egg surface. Results from our laboratory have shown that this binding ability resides in a 12-amino-acid region corresponding to a highly conserved motif of the CRISP family, named Signature 2 (S2). In addition to this, our results revealed that CRISP1 could also be involved in the previous step of sperm binding to the zona pellucida, identifying a novel role for this protein in fertilization. As another approach to elucidate the participation of CRISP1 in fertilization, a mouse line containing a targeted disruption of CRISP1 was generated. Although CRISP1-defi cient mice exhibited normal fertility, CRISP1-deffi cient sperm presented a decreased level of protein tyrosine phosphorylation during capacitation, and an impaired ability to fertilize both zona-intact and zonafree eggs in vitro, confi rming the proposed roles for the protein in fertilization. Evidence obtained in our laboratory indicated that testicular CRISP2 would also be involved in sperm-egg fusion. Competition assays between CRISP1 and CRISP2, as well as the comparison of their corresponding S2 regions, suggest that both proteins bind to common complementary sites in the egg. Together, these results suggest a functional cooperation between CRISP1 and CRISP2 to ensure the success of fertilization.

The protein and transcript profiles of human semen

“…The absence of testes-support cell-related proteins and the enrichment of exosomal proteins reinforces the notion of seminal fluid and spermatozoa communication through the exosomes released by the accessory sex glands. Whereas the majority of proteins related to the interaction of sperm with the zona pellucida are sperm-specific, e.g., IZUMO1 (Chalbi et al 2014), approximately one-quarter, e.g., zona pellucida binding protein (Lin et al 2007), heat shock-related 70-kDa protein 2 (Nixon et al 2015) and cysteine-rich secretory proteins 1 and 2 (reviewed in Cohen et al 2011), were identified in both sperm and seminal plasma proteomes. This suggests that some proteins that may play a role in sperm-egg recognition or interaction could be acquired externally from the seminal fluid.…”

Biochemical and structural characterization of a protein complex containing a hyaluronidase and a CRISP-like protein isolated from the venom of the spider Acanthoscurria natalensis

“…CRISPs represent an extensive family of highly conserved cysteine-rich secretory proteins, comprising three main groups, named CRISP-1, CRISP-2 and CRISP-3 [8]. The main biological functions related to CRISP-1 and CRISP-2 include ion channels blocking and involvement in the processes of gametes maturation and fusion, being in this case mediated by a motif named signature 2 [9]. CRISP-3 is found in blood plasma and exocrine secretions and its role in…”

Multiomics analysis of the giant triton snail salivary gland, a crown-of-thorns starfish predator

“…The cysteine-rich venom proteins (CRVPs) belong to the larger family of proteins known as the cysteine-rich secretory proteins (CRISPs), and are found in the venoms of diverse species, including snakes, cone snails, coleoids, stinging insects, scorpions and spiders [82][83][84][85][86][87][88] . Proteins from this family are also commonly found in the mammalian male reproductive tract 89 and are associated with a broad range of functions, such as fertilization and sperm-egg interaction 86,88 . In the current study, 8 transcripts that encode venom-like CRISPs were identified within the SG-AL, and 2 were confirmed through proteomic analysis ( Table 2).…”