Galactosyltransferase function during mammalian fertilization

Gamete recognition has been studied extensively in the mouse. In this syste m, it is generally believed that sperm bind to a class of O-linked oligosac charides on the zona pellucida glycoprotein, ZP3. The best characterized sp erm receptor for ZP3 is beta1,4-galactosyltransferase [GalT], which functio ns in a lectin-like capacity by binding to N-terminal N-acetylglucosamine r esidues on ZP3 oligosaccharides. Multivalent oligosaccharides on ZP3, as we ll as synthetic polymers terminating in N-acetylglucosamine aggregate GalT, leading to activation of a heterotrimeric G protein cascade and culminatin g in the acrosome reaction. Following fertilization, cortical granules rele ase N-acetylglucosaminidase, which removes the binding site for sperm GalT and facilitates the zona block to polyspermic binding. Genetic manipulation of GalT expression has confirmed its function as a ZP3 receptor. Overexpre ssing GalT on sperm leads to increased binding of ZP3, increased G protein activation, and precocious acrosome reactions. In contrast, sperm from mice made null for GalT by homologous recombination are refractory to ZP3, in t hat they are unable to bind soluble ZP3 and fail to undergo the acrosome re action in response to zona glycoproteins. Surprisingly, GalT null sperm sti ll bind to the zona and achieve low rates of fertilization in vitro. This t hen suggests that sperm-egg binding involves receptor-ligand interactions i ndependent of GalT and ZP3. The current model suggests that GalT functions as the ZP3 receptor that is responsible for inducing the acrosome reaction, whereas initial sperm-zona binding is dictated by other sperm surface rece ptors. Consistent with this, at least three other zona pellucida monosaccha rides have been implicated in sperm binding, and novel sperm surface glycop roteins have been suggested to function in gamete binding. A large scaffold ing protein has been identified that associates with the GalT cytoplasmic d omain and may be responsible for orchestrating its signal transduction capa cities that lead to the acrosome reaction. Copyright (C) 2001 S. Karger AG, Basel.