My laboratory is studying the molecular basis of fertilization in the mouse. Using a variety of biochemical, immunological and genetic probes, we have recently shown that initial gamete recognition between the sperm surface and the egg zona pellucida is mediated, at least in part, by the binding of a sperm surface enzyme, galactosyltransferase (GalTase) to its complementary substrate in the zona pellucida. GalTase is present on the cell surface throughout all stages of spermatogenesis, during which time it becomes redistributed from an initially diffuse and uniform distribution on primary spermatocytes to its final location on mature sperm overlying a discrete portion of the intact acrosome. Before sperm are able to bind the zona pellucida, they must first release a large molecular weight competitive GalTase substrate, which is occupying the zona binding site. Sperm binding to the zona pellucida induces the completion of the acrosome reaction, and recent findings show that despite the loss of the relevant plasma membrane domain, the GalTase is redistributed to the lateral sperm surface, presumably for some subsequent function. In this proposal we will more rigorously define the association of the GalTase with the sperm surface, purify the enzyme to apparent homogeneity and characterize its substrate specificity. The complementary substrate in the zona pellucida for the sperm GalTase will be identified and compared to the zona receptor for sperm identified by other workers. We will determine if fertilization inactivates the zona substrate for the sperm GalTase, leading to the zona block to polyspermy. Experiments will determine if the GalTase, leading to the zona block to polyspermy. Experiments will determine if the GalTase on the surface of early spermatogenic cells participates during germ cell adhesion to the Sertoli epithelium. Finally, we will examine some possible functions of the GalTase redistributed on acrosome- reacted sperm following initial sperm-zona binding. These experiments will give us more insight into the molecular nature of mouse gamete receptors, how they are modified during fertilization, and what other possible functions they may serve both before and after initial sperm-egg binding.

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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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University of Texas MD Anderson Cancer Center
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United States
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Joseph, Avenel; Shur, Barry D; Hess, Rex A (2011) Estrogen, efferent ductules, and the epididymis. Biol Reprod 84:207-17
Raymond, Adam S; Elder, Brooke; Ensslin, Michael et al. (2010) Loss of SED1/MFG-E8 results in altered luminal physiology in the epididymis. Mol Reprod Dev 77:550-63
Joseph, Avenel; Hess, Rex A; Schaeffer, David J et al. (2010) Absence of estrogen receptor alpha leads to physiological alterations in the mouse epididymis and consequent defects in sperm function. Biol Reprod 82:948-57
Joseph, Avenel; Shur, Barry D; Ko, CheMyong et al. (2010) Epididymal hypo-osmolality induces abnormal sperm morphology and function in the estrogen receptor alpha knockout mouse. Biol Reprod 82:958-67
Raymond, Adam; Ensslin, Michael A; Shur, Barry D (2009) SED1/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions. J Cell Biochem 106:957-66
Raymond, Adam S; Shur, Barry D (2009) A novel role for SED1 (MFG-E8) in maintaining the integrity of the epididymal epithelium. J Cell Sci 122:849-58
Lyng, Robert; Shur, Barry D (2009) Mouse oviduct-specific glycoprotein is an egg-associated ZP3-independent sperm-adhesion ligand. J Cell Sci 122:3894-906
Copland, Susannah D; Murphy, Ana A; Shur, Barry D (2009) The mouse gamete adhesin, SED1, is expressed on the surface of acrosome-intact human sperm. Fertil Steril 92:2014-9
Shur, Barry D (2008) Reassessing the role of protein-carbohydrate complementarity during sperm-egg interactions in the mouse. Int J Dev Biol 52:703-15
Ensslin, Michael A; Lyng, Robert; Raymond, Adam et al. (2007) Novel gamete receptors that facilitate sperm adhesion to the egg coat. Soc Reprod Fertil Suppl 63:367-83

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