My laboratory is interested in the molecular basis of cellular interactions during mammalian fertilization and development. Our previous studies have identified a novel sperm surface receptor. galactosyltransferase(GalTase), that facilitates gamete recognition by binding to its specific oligosaccharide ligand on the extracellular coat of the egg. Although GalTase is traditionally viewed as an intracellular biosynthetic enzyme, we now know that an isozymic variant of GalTase is expressed on the cell surface due, in part, to a unique cytoplasmic sequence that overrides the Golgi retention- signal, transporting GalTase to the cell surface. The purpose of this renewal application is to continue our analysis of GalTase function during fertilization in the mouse. Thus far, HD 23479 has supported the work reported in 14 peer-reviewed publications, the results of which can be summarized as follows. GalTase is first expressed on the germ cell surface during early spermatogenesis, where it may function during germ cell adhesion to Sertoli cells. In the epididymis, soluble glycosides bind to the sperm surface, masking GalTase. These competitive glycosides are shed from the sperm surface during capacitation. thus exposing the GalTase binding site for interaction with its ligand on the egg coat glycoprotein, ZP3. Aggregation of GalTase by multivalent ZP3 oligosaccharides activates a heterotrimeric 0-protein cascade, leading to the acrosome reaction. The acrosome releases hydrolytic enzymes. including N-acetylglucosaminidase. that facilitates sperm penetration through the zona. After egg activation, the global release of N-acetylglucosaminidase from the cortical granules destroys the GalTase recognition site on ZP3, thus leading to the block in polyspermic binding. In this renewal application, we wish to address GalTase function in light of other sperm proteins with which it may associate. We intend to: I) examine the effect of ZP3 binding on the phosphorylation of the GalTase cytoplasmic domain, 2) identify the kinase responsible for phosphorylating sperm GalTase, 3) examine the effects of phosphorylation on 0-protein activation and identify amino acid residues within the cytoplasmic domain responsible for G-protein activation, 4) identify the repertoire of sperm proteins that constitute the signal transduction complex in association with the GalTase cytoplasmic domain, 5) determine whether the cytoplasmic domain of sperm GalTase defines a novel class of testis-specific receptors, and 6) examine whether the extracellular domain of sperm GalTase complexes with other membrane proteins that may also contribute to ZP3 binding.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Tasca, Richard J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Joseph, Avenel; Shur, Barry D; Hess, Rex A (2011) Estrogen, efferent ductules, and the epididymis. Biol Reprod 84:207-17
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 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
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

Showing the most recent 10 out of 39 publications