Fertilization and embryo development Opinion

Clark, F.Gary; Oehninger, Sergio; Seppälä, Markku

doi:10.1093/molehr/2.7.513

Cited by 26 publications

(6 citation statements)

References 31 publications

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“…It has been observed that mouse sperm cells bind very tightly to rabbit erythrocytes, but not to human, mouse, rat, goat, sheep, cow, horse, dog, or cat erythrocytes. 60 Analysis of rabbit erythrocyte glycans by mass spectrometry indicates an abundance of bi-antennary complex N-glycans terminated with repeating Gal-β1,4-GlcNAc moieties 61 , which might enhance the lytic activity of VCC towards these cells. Staphylococcal α-hemolysin also shows a preference for rabbit erythrocytes over human; however, this partiality is mediated by binding of the metalloprotease ADAM-10.…”

Section: Discussionmentioning

confidence: 99%

Vibrio cholerae Cytolysin Recognizes the Heptasaccharide Core of Complex N-Glycans with Nanomolar Affinity

Levan

Olson

2013

Journal of Molecular Biology

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Pathogens selectively target host cells using adhesion molecules and secreted virulence factors that may utilize protein, lipid, or carbohydrate ligands on the cell surface. The human intestinal pathogen Vibrio cholerae secretes a pore-forming toxin, Vibrio cholerae cytolysin (VCC), which contains two domains that are structurally similar to known carbohydrate-binding proteins. These tandem domains are attached to the carboxy-terminus of the cytolytic domain and contain a β-trefoil fold and a β-prism fold. VCC has been shown to bind glycosylated proteins, and removal of the β-prism domain leads to a large decrease in lytic activity against rabbit erythrocytes. Despite these clues, the identity of the glycan receptors of VCC and the role of glycan binding in toxin activity remains unknown. To better understand this specificity, we used a combination of structural and functional approaches to characterize the carbohydrate-binding activity of the VCC toxin. We first probed the monosaccharide-binding activity of VCC and demonstrated that the toxin exhibits millimolar affinity for aldohexoses. To understand this specificity, we solved the crystal structure of the VCC β-prism domain bound to methyl-α-mannose. Next, we utilized a mammalian glycan screen to determine that the β-prism domain preferentially binds complex N-glycans with a heptasaccharide GlcNAc4 Man3 core (NGA2). Fluorescence anisotropy and surface plasmon resonance indicated an approximately 100-nanomolar affinity of the β-prism domain for the heptasaccharide core. Our results suggest that carbohydrate-binding domains on the VCC toxin facilitate high-affinity targeting of mammalian cell membranes, which may contribute to the ability of VCC to lyse cells at picomolar concentrations.

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Section: Discussionmentioning

confidence: 99%

Vibrio cholerae Cytolysin Recognizes the Heptasaccharide Core of Complex N-Glycans with Nanomolar Affinity

Levan

Olson

2013

Journal of Molecular Biology

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“…Electron microscopy of sperm-erythrocyte interaction indicates that this binding is between the plasma membranes of 3 A. Thall, personal communication. the two cell types (50). Periodate oxidation of rabbit erythrocytes (10 mM NaIO 4 , 0.15 M NaCl, 1 h, 23°C) results in a Ͼ98% reduction in binding.…”

Section: Discussionmentioning

confidence: 99%

Structural Analysis of Murine Zona Pellucida Glycans

Easton¹,

Patankar²,

Lattanzio³

et al. 2000

Journal of Biological Chemistry

103

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Murine sperm initiate fertilization by binding to specific oligosaccharides linked to the zona pellucida, the specialized matrix coating the egg. Biophysical analyses have revealed the presence of both high mannose and complex-type N-glycans in murine zona pellucida. The predominant high mannose-type glycan had the composition Man 5 GlcNAc 2 , but larger oligosaccharides of this type were also detected. Biantennary, triantennary, and tetraantennary complex-type N-glycans were found to be terminated with the following antennae: Gal␤1-4GlcNAc, NeuAc␣2-3Gal␤1-4GlcNAc, NeuGc␣2-3Gal␤1-4GlcNAc, the Sd a antigen (NeuAc␣2-3[GalNAc␤1-4]Gal-␤1-4GlcNAc, NeuGc␣2-3[GalNAc␤1-4]Gal␤1-4GlcNAc), and terminal GlcNAc. Polylactosamine-type sequence was also detected on a subset of the antennae. Analysis of the O-glycans indicated that the majority were core 2-type (Gal␤1-4GlcNAc␤1-6[Gal␤1-3]GalNAc). The ␤1-6-linked branches attached to these O-glycans were terminated with the same sequences as the N-glycans, except for terminal GlcNAc. Glycans bearing Gal␤1-4GlcNAc␤1-6 branches have previously been suggested to mediate initial murine gamete binding. Oligosaccharides terminated with GalNAc␤1-4Gal have been implicated in the secondary binding interaction that occurs following the acrosome reaction. The significant implications of these observations are discussed.The initial event in the life of all sexually reproducing metazoans is the fertilization of an individual egg by a single sperm. Murine sperm begin this process by binding to the specialized extracellular matrix of the egg known as the mZP 1 (1). This matrix has been shown to be composed of three major glycoproteins (designated mZP1, mZP2, and mZP3) (2). There is strong evidence to suggest that binding occurs via the interaction of mZP3-associated glycans with lectin-like proteins on the sperm surface (3, 4) that in turn induce a signal transduction event known as the acrosome reaction (5). During this reaction, the plasma membrane of the sperm fuses with the outer membrane of a lysosome-like organelle known as the acrosome lying just beneath the surface of the sperm. The resulting membrane complex then blebs off to expose the inner acrosomal membrane. In the mouse model, this inner acrosomal membrane then undergoes secondary binding to mZP2. Sperm move through the mZP and fuse with the egg, thus completing the process of fertilization.Initial studies performed by Wassarman and co-workers (3) indicate that either Pronase glycopeptides (3) or O-linked oligosaccharides (4) obtained from mZP3 block murine sperm-egg binding. Several major models for the initial murine gamete binding interaction have subsequently been proposed that are based upon specific carbohydrate recognition (6 -9). A recent study involving recombinant mZP3 synthesized in murine F9 embryonal carcinoma cells suggests that vicinal presentation of O-linked oligosaccharides within a specific region of mZP3 is necessary for initial sperm-egg binding (10). mZP2 has been proposed to be the glycoprotein that mediates...

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“…The initial events of murine fertilization involve both sperm binding and the induction of the acrosome reaction. The binding of murine sperm to rabbit erythrocytes clearly does not induce the acrosome reaction (44), suggesting that the signal transduction event that triggers this reaction is not carbohydrate-mediated. Thus the binding of a currently unidentified signal transduction molecule or complex on murine sperm to mZP3 may be essential for inducing the acrosome reaction.…”

Section: Potential For Redundant Carbohydrate-protein and Protein-promentioning

confidence: 96%

“…2) (13), mZP N-glycans (48), and rabbit erythrocytes following exhaustive digestion with ␣-galactosidase. Based on this overlap, the ␤1-6-linked LacNAc sequence was proposed to be the major carbohydrate ligand recognized during murine gamete binding (44).…”

Section: A Model For Carbohydrate-dependent Adhesionmentioning

confidence: 99%

Molecular Models for Murine Sperm-Egg Binding

Clark

Dell

2006

Journal of Biological Chemistry

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Murine sperm initiate fertilization by binding to the specialized extracellular matrix of mouse eggs, known as the zona pellucida. Over the past decade, powerful genetic, biophysical, and biochemical techniques have been employed to gain new insights into this interaction. Evidence from these studies does not support either of two major models for binding first proposed over two decades ago. Two more recently established models suggest that protein-protein interactions predominate during this initial stage of fertilization. Another model proposes that about 75-80% of the murine sperm bound to zona pellucida under well defined in vitro conditions is carbohydrate dependent, with the remaining sperm bound via protein-protein interactions. Mounting evidence suggests that the carbohydrate sequences coating the murine egg could be employed as specific immune recognition markers. Continued investigation of this system may resolve many of these controversial findings and reveal novel functions for murine zona pellucida glycoproteins.The species-specific binding of sperm to eggs is the initial event in the development of metazoans that propagate solely via sexual reproduction. Considerable evidence indicates that carbohydrate recognition plays a key role in this interaction in lower species (reviewed in Refs. 1-3), eutherian mammals (4, 5), and marsupials (6).The major animal model for investigating the role of carbohydrate recognition in mammalian fertilization is the mouse. This species is preferred because of its fecundity, short life span, low maintenance costs, and its ability to be genetically manipulated. Murine sperm initiate fertilization by binding to the mZP, 3 a matrix composed of three major glycoproteins designated mZP1, mZP2, and mZP3 (7). mZP3 has been implicated as the component that mediates both initial binding and the induction of the acrosome reaction (8). Its genetic deletion leads to the complete loss of a functional mZP and infertility (9). Therefore mZP3 is usually the primary glycoprotein targeted in functional studies. The Emergence of Major Models for Murine Sperm-Egg BindingTwo major hypothetical models for murine gamete binding were first presented in 1985. The resistance of mZP3 to denaturing conditions suggested that its protein-linked glycans could be responsible for initial sperm-egg binding (10). Subsequent studies demonstrated that either glycopeptides or O-linked glycans derived from mZP3 inhibit murine sperm-egg binding in a competitive murine sperm-egg binding assay (10, 11). Therefore Wassarman and colleagues suggested that EBPs on the sperm plasma membrane interact with mZP3 associated O-glycans to mediate initial murine sperm-egg binding.Digestion of the O-glycans derived from mZP3 with ␣-galactosidase results in the loss of their inhibitory activity in the murine sperm-egg binding assay, suggesting that terminal Gal␣1-3Gal sequence are crucial for binding (12). However, a later study confirmed that both terminal ␤l-4-linked Gal and its ␣1-3-galactosylated analogue (Gal␣1-3Gal␤1-...

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Fertilization and embryo development Opinion

Cited by 26 publications

References 31 publications

Vibrio cholerae Cytolysin Recognizes the Heptasaccharide Core of Complex N-Glycans with Nanomolar Affinity

Vibrio cholerae Cytolysin Recognizes the Heptasaccharide Core of Complex N-Glycans with Nanomolar Affinity

Structural Analysis of Murine Zona Pellucida Glycans

Molecular Models for Murine Sperm-Egg Binding

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