Journal article
Epididymal secreted protein Crisp-1 and sperm function
Molecular and cellular endocrinology, Vol.250(1), pp.122-127
2006
Handle:
https://hdl.handle.net/2376/105615
PMID: 16414181
Abstract
Crisp-1 is a member of the cysteine-rich secretory protein family. This family of proteins is characterized by the presence of 16 conserved cysteine residues, the characteristic from which the family name is derived. Members of the Crisp protein family are found in the secretions of the reproductive tract and salivary glands, including venom toxins from several species of snakes and lizards. The Crisp proteins are modular, each containing an amino terminal pathogenesis-related (PR)-like domain and a carboxyl terminal cysteine-rich domain (CRD) connected by a hinge region. Sequence and structural similarities to proteins with known functions suggest that the Crisp family of proteins may act by regulating cellular ion channels. Rat Crisp-1 is synthesized as two distinct isoforms (referred to as Proteins D and E) by the epididymal epithelium and both are secreted into the luminal fluid where they interact with spermatozoa. Our laboratory has correlated Crisp-1 binding to sperm with inhibiting the signaling cascades that initiate capacitation while others have shown that blocking Crisp-1 binding sites on oocytes interferes with sperm–egg fusion. We hypothesize that the D and E populations of rat Crisp-1 have different interactions with sperm that modulate these distinct biological activities. Through tandem mass spectrometry (MS/MS) and monosaccharide composition analyses, we have identified at least one difference between the D and E forms as an additional single O-linked
N-acetyl galactosamine on an amino terminal threonine residue in Protein E. This post-translational modification appears to account for the unique ‘E’ epitope bound by monoclonal antibody 4E9 developed in our laboratory, and may also lead to differential processing and localization of Protein E on sperm, when compared to Protein D. These findings are the first step in distinguishing the molecular basis of the biological activities of the D and E forms of rat Crisp-1. The epididymal-specific expression of Crisp-1, combined with its role in regulation of sperm capacitation and oocyte interaction, make it an attractive target for post-testicular contraceptive development.
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Details
- Title
- Epididymal secreted protein Crisp-1 and sperm function
- Creators
- Kenneth P Roberts - Department of Urologic Surgery, University of Minnesota, 420 Delaware St. SE, MMC 394, Minneapolis, MN, United StatesKathy M Ensrud - Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, United StatesJoseph L Wooters - Biological Technologies, Molecular Profiling and Biomarker Discovery, Wyeth Research, Cambridge, MA, United StatesMichael A Nolan - Contraception, Women's Health & Musculoskeletal Biology, Wyeth Research, Collegeville, PA, United StatesDaniel S Johnston - Contraception, Women's Health & Musculoskeletal Biology, Wyeth Research, Collegeville, PA, United StatesDavid W Hamilton - Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, United States
- Publication Details
- Molecular and cellular endocrinology, Vol.250(1), pp.122-127
- Academic Unit
- Elson S. Floyd College of Medicine
- Publisher
- Elsevier Ireland Ltd
- Identifiers
- 99900547076001842
- Language
- English
- Resource Type
- Journal article