Molecular Basis of Mammalian Gamete Binding

Abstract

Despite the importance of fertilization for controlling human reproduction, regulating animal production, and promoting preservation of endangered species, the molecular basis underlying gamete binding and fertilization has been perplexing. More progress has been made in the mouse than in other mammals and, recently, targeted deletion of specific genes in the mouse has yielded intriguing results. This review will emphasize research performed by our laboratory and others done primarily with mouse gametes but will include some interesting observations from other mammals. Studies of murine fertilization indicate that oligosaccharides on the egg coat glycoprotein ZP3 bind sperm. The precise oligosaccharides that bind sperm are the subject of considerable debate. ZP3 also induces exocytosis of the sperm acrosome, allowing sperm to penetrate through the egg coat (zona pellucida). A number of candidate ZP3 receptors have been proposed and studies of ␤1,4galacto-syltransferase-I (GalT-I) are reviewed here in the most detail. Sperm from mice with a targeted deletion of GalT-I still are able to bind the zona pellucida but are unable to acrosome react and penetrate through the zona. Therefore, the unique role of GalT-I appears to be in signal transduction. GalT-I forms a complex with heterotrimeric G proteins and activates signaling, leading to exocytosis in sperm and in heterologous cells expressing GalT-I. Other signaling steps triggered by GalT-I are under active investigation; this receptor forms a complex with a protein kinase anchoring protein.After exocytosis of the acrosome, sperm penetrate the zona pellucida and fuse with the oocyte plasma membrane using ADAM family members on sperm and integrins on oocytes. These proteins, along with the tetraspanins on oocytes, may form a complex web at gamete fusion. Targeted deletion of specific genes in this putative complex has provided important information about their redundancy. After the oocyte is fertilized, the binding site for GalT-I is lost from ZP3, preventing additional sperm from binding to the zona pellucida. New technical advances and creative ideas offer the opportunity to make important advances and to solve the conundrum of fertilization.

Glycosidases in the plasma membrane of Ceratitis capitata spermatozoa

“…Moreover, the presence of a-L-fucosidase on the plasma membrane over the acrosome rules out the possibility that also this glycosidase might be involved in the primary binding between sperm and egg, as hypothesized in D. melanogaster . The presence on the surface of Ceratitis sperm of several glycosidases that might interact with complementary glycoconjugates of the egg surface (manuscript in preparation) is not surprising, since several authors have hypothesized that more than one receptor is involved and that the spermeegg binding is regulated by the sum of several molecular interactions (Wassarman et al, 2001;Miller et al, 2002;Lyng and Shur, 2007). Future experiments will provide to determine whether also in C. capitata b-N-acetylhexosaminidase, a-L-fucosidase and a-mannosidase are involved in spermeegg interactions and this work represents a starting point to unravel the precise role played by these glycosidases in gamete recognition in the Tephritidae family.…”

“…It has been demonstrated that in the early gamete recognition glycosidases and glycosyltransferases are the first receptors for the egg surface both in vertebrates and in invertebrates (Hoshi et al, 1983(Hoshi et al, , 1985Hoshi, 1984;Tulsiani et al, 1997;Martinez et al, 2000;Mengerink and Vacquier, 2001;Koyanagi and Honegger, 2003;Zitta et al, 2006;Lyng and Shur, 2007). In particular, in mammals, it has been indicated that several other proteins of the sperm surface, such as proteases, tyrosine kinases, phospholipase, may also function as receptors for the egg zona pellucida (Mengerink and Vacquier, 2001;Wassarman et al, 2001;Miller et al, 2002;Talbot et al, 2003;Shur et al, 2006).…”

Protease activity involvement in the passage of mammalian sperm through the zona pellucida

“…It is not clear yet which sugars are involved in this interaction, but in vitro studies have suggested that it is stereo specifi c, with the participation of polysulphated sugar residues (Jones, 1991;Lo Leggio et al, 1994). One is a terminal β-1,3 galactose (Bleil and Wassarman, 1988) and the other is a terminal N-acetylglucosamine proposed to bind β-1,4 galactosyl transferase, a putative sperm receptor (Miller and Ax, 1990;Miller et al, 2002). Furthermore, the continued fertility of mutant mice lacking either the enzyme that adds terminal β-1,3 galactose (Thall et al, 1995)or b-1,4 galactosyltransferase (Shi et al, 2001) makes it unlikely that these are the sole determinants of mouse sperm binding.…”

Drosophila sperm surface alpha-l-fucosidase interacts with the egg coats through its core fucose residues

“…Gamete binding in many species has been proposed to involve interactions between proteins on sperm and glycoconjugates on the egg surface (Mengerink and Vacquier, 2001;Evans, 2012;Clark, 2013Clark, , 2014. In particular, experimental evidence suggest that sperm surface glycosidases could act in a non-catalytic or lectinlike manner, recognizing complementary sugar moieties in the egg envelope (Miranda et al, 2000;Martinez et al, 2000;Perotti et al, 2001;Miller et al, 2002;Intra et al, 2006;Zitta et al, 2006;Hedrick, 2008;Honegger and Koyanagi, 2008;Intra et al, 2011). Examples of glycosidases on the sperm plasma membrane include mannosidases and fucosidases in mammalian sperm (Tulsiani et al, 1989(Tulsiani et al, , 1990Venditti et al, 2010;Phopin et al, 2012Phopin et al, , 2013, fucosidases and N-acetylglucosaminidases in tunicates (Hoshi et al, 1983(Hoshi et al, , 1985(Hoshi et al, , 1994Hoshi, 1986;Godknecht and Honegger, 1991;Matsumoto et al, 2002;Downey and Lambert, 1994), and mannosidases, fucosidases and N-acetylglucosaminidases in flies (Cattaneo et al, 1997(Cattaneo et al, , 2002Pasini et al, 1999;Perotti et al, 2001;Intra et al, 2006Intra et al, , 2009Intra et al, , 2011.…”