Abstract

Funds are requested to study the specific functions of the Crisp-1 protein. Crisp-1 is produced in the epididymis and associates with the sperm during transit through the organ. The high similarity to a known ryanodine receptor agonist suggests that Crisp-1 may have a role in ion channel regulation. Changes in calcium concentrations are required for sperm to become capacitated and undergo the acrosome reaction in preparation for fertilization. In vitro capacitation studies of rat sperm show that when Crisp-1 is present, sperm are prohibited from capacitating.
The specific aims focus on determining the mechanisms involved in the inhibition of capacitation by Crisp-l, identification of the receptor for Crisp-1 on sperm, identification of the Crisp-1 active site, and investigation of the ability of other members of the Crisp family to mimic the actions of Crisp-1. Crisp-1 will also be tested for its ability to inhibit capacitation and the acrosome reaction in human sperm. Finally, potential actions of Crisp-1 on the egg, such as the ability to regulate cortical granule fusion, will be examined. The proposed studies will provide significant contributions to our understanding of sperm function and may also have potential application to male infertility and contraceptive development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD011962-26
Application #
7210587
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Rankin, Tracy L
Project Start
1978-09-29
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
26
Fiscal Year
2007
Total Cost
$253,449
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Liu, Mian; Hamilton, David W; Barany, George (2010) Solid-phase synthesis and evaluation of glycopeptide fragments from rat epididymal cysteine-rich secretory protein-1 (Crisp-1). Molecules 15:6399-410
Roberts, Kenneth P; Ensrud-Bowlin, Kathy M; Piehl, Laura B et al. (2008) Association of the protein D and protein E forms of rat CRISP1 with epididymal sperm. Biol Reprod 79:1046-53
Roberts, Kenneth P; Johnston, Daniel S; Nolan, Michael A et al. (2007) Structure and function of epididymal protein cysteine-rich secretory protein-1. Asian J Androl 9:508-14
Roberts, Kenneth P; Wamstad, Joseph A; Ensrud, Kathy M et al. (2003) Inhibition of capacitation-associated tyrosine phosphorylation signaling in rat sperm by epididymal protein Crisp-1. Biol Reprod 69:572-81
Roberts, Kenneth P; Ensrud, Kathy M; Hamilton, David W (2002) A comparative analysis of expression and processing of the rat epididymal fluid and sperm-bound forms of proteins D and E. Biol Reprod 67:525-33
Roberts, K P; Hoffman, L B; Ensrud, K M et al. (2001) Expression of crisp-1 mRNA splice variants in the rat epididymis, and comparative analysis of the rat and mouse crisp-1 gene regulatory regions. J Androl 22:157-63
Klemme, L M; Roberts, K P; Hoffman, L B et al. (1999) Cloning and characterization of the rat Crisp-1 gene. Gene 240:279-88
Xu, W; Ensrud, K M; Hamilton, D W (1997) The 26 kD protein recognized on rat cauda epididymal sperm by monoclonal antibody 4E9 has internal peptide sequence that is identical to the secreted form of epididymal protein E. Mol Reprod Dev 46:377-82
Xu, W; Hamilton, D W (1996) Identification of the rat epididymis-secreted 4E9 antigen as protein E: further biochemical characterization of the highly homologous epididymal secretory proteins D and E. Mol Reprod Dev 43:347-57
Siiteri, J E; Ensrud, K M; Moore, A et al. (1995) Identification of osteopontin (OPN) mRNA and protein in the rat testis and epididymis, and on sperm. Mol Reprod Dev 40:16-28

Showing the most recent 10 out of 24 publications