Sperm require β-<i>N</i>-acetylglucosaminidase to penetrate through the egg zona pellucida

Miller, David J.; Gong, Xianghui; Shur, Barry D.

doi:10.1242/dev.118.4.1279

Cited by 118 publications

(8 citation statements)

References 42 publications

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“…Each glycoprotein contains glycans covalently linked to asparagine (N-linked) and/or serine and threonine (O-linked) . Previous studies indicated that the adhesion of sperm to the egg is mainly mediated by a specific interaction of sperm surface molecules with the glycan moieties on the ZP. − Glycosidase digestion and mass spectrometric analyses have indicated that several mouse ZP3 terminal monosaccharide residues, including β- N -acetylgalactosamine (GalNAc), β- N -acetylglucosamine (GlcNAc), mannose, galactose, and sialyl, may be critical for sperm binding to the ZP. Although a fucosylated glycan was identified on human ZP and the addition of a fucose residue to the GlcNAc and galactose trisaccharides enhances mouse sperm–egg binding affinity, the participation of fucose in mouse gamete binding is not definitive.…”

mentioning

confidence: 99%

Fucose, Mannose, and β-N-Acetylglucosamine Glycopolymers Initiate the Mouse Sperm Acrosome Reaction through Convergent Signaling Pathways

Sampson

2013

ACS Chem. Biol.

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The sperm acrosome reaction (AR), an essential exocytosis step in mammalian fertilization, is mediated by a species-specific interaction of sperm surface molecules with glycans on the egg. Previous studies indicate that a subset of terminal carbohydrates on the mouse egg zona pellucida (ZP) trigger the AR by cross-linking or aggregating receptors on the sperm membrane. However, the exact role of those carbohydrates in AR has not been identified and the mechanism underlying the AR still needs further investigation. To study this process, a series of glycopolymers was synthesized. The glycopolymers are composed of a multivalent scaffold (norbornene), a functional ligand (previously identified ZP terminal monosaccharides), and a linker connecting the ligand and the scaffold. The polymers were tested for their ability to initiate AR and through which signaling pathways AR induction occurred. Our data demonstrate that mannose, fucose, and β-N-acetylglucosamine 10-mers and 100-mers initiate AR in a dose-dependent manner, and the 100-mers are more potent on a per monomer basis than the 10-mers. Although nearly equipotent in inducing the AR at the optimal concentrations, their AR activation kinetics are not identical. Similar to mouse ZP3, all 100-mer-activated AR are sensitive to guanine-binding regulatory proteins (G-proteins), tyrosine kinase, protein kinase A, protein kinase C, and Ca2+-related antagonists. Thus, the chemotypes of synthetic glycopolymers imitate the physiologic AR-activation agents and provide evidence that occupation of one of at least three different receptor binding sites is sufficient to initiate the AR.

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confidence: 99%

Fucose, Mannose, and β-N-Acetylglucosamine Glycopolymers Initiate the Mouse Sperm Acrosome Reaction through Convergent Signaling Pathways

Sampson

2013

ACS Chem. Biol.

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“…Enzymes observed in semen might play several roles; for example, AcP in mammals takes part in the conversion of proacrosin to acrosin [20], β-NAGase is associated with the acrosome, and its inhibition in mouse sperm results in a lower percentage of fertilised eggs [21]. Our earlier experiment revealed that the AcP present in ide and sturgeon sperm might have an active role in egg fertilisation [8,9], but we also observed no effect of ammonium molybdate addition during carp fertilisation (Sarosiek, unpublished data).…”

Section: Effect Of Inhibitors On Enzymatic Activities Sperm Motility ...mentioning

confidence: 99%

Optimalisation of the Activation Medium and Effect of Inhibiting Activities of Acid Phosphatase, Lactate Dehydrogenase and β-N-Acetylglucosaminidase on the Fertilisation Success of Eurasian Perch (Perca fluviatilis L.)

Sarosiek

Dryl

Kowalski

et al. 2022

Animals

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Although methods for the artificial reproduction of perch have been developed, a lack of information remains regarding the enzymes present in its semen, as well as their role in the fertilisation process. In this study, we first select the optimal activating solution for perch fertilisation and then determine the inhibition effect of enzymes that have already been reported as present in the sperm of teleosts—acid phosphatase (AcP), lactic dehydrogenase (LDH) and β-N-acetylglucosaminidase (β-NAGase)—on the percentage of motile spermatozoa and fertilised eggs. Of the 8 studied activation media, a solution composed of 80 mM NaCl, 20 mM KCl, 10 mM Tris, with pH 8.0 and 206 mOsm/kg proved to be optimal for perch gametes. The addition of ammonium molybdate (AcP inhibitor) caused no significant reduction in the percentage of fertilised eggs. On the other hand, the addition of 0.25 mM gossypol (LDH inhibitor) and 0.125 M acetamide (β-N-acetylglucosaminidase inhibitor) significantly decreased the fertilisation percentage to 41.1% and 52.4%, respectively, in contrast to the control (89.9 %). Both LDH and β-NAGase thus seem to play a very important role in the perch fertilisation process.

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“…It has been previously established that PUGNAc 2 is a potent competitive inhibitor of both O-GlcNAcase 3,26 and bhexosaminidase. 18, 25 For the human enzymes the respective K I values are 46 nM and 36 nM. 3, 21 As described above, selective inhibitors of these enzymes are of interest and we therefore evaluated the selectivity of putative inhibitors 16a-f.…”

Section: Inhibition Studiesmentioning

confidence: 99%

“…O-(2-Acetamido-2-deoxy-D-glucopyranosylidene)amino Nphenylcarbamate (PUGNAc) 18,28 2 is another compound that suffers from the same problem of lack of selectivity, yet has enjoyed use as an inhibitor of both human O-GlcNAcase 3, 26 and the family 20 human b-hexosaminidases. 25 This molecule, developed by Vasella and coworkers, was found to be a potent competitive inhibitor of the b-N-acetyl-glucosaminidases from Canavalia ensiformis, Mucor rouxii, and the b-hexosaminidase from bovine kidney. 18 One rationale for the potency of PUGNAc 2 toward both the family 84 O-GlcNAcases and the family 20 b-hexosaminidases is the sp 2 hybridisation of the anomeric carbon.…”

Section: Introductionmentioning

confidence: 99%

A divergent synthesis of 2-acyl derivatives of PUGNAc yields selective inhibitors of O-GlcNAcase

2006

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A divergent route facilitating the rapid synthesis of a series of O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenylcarbamate (PUGNAc)-based inhibitors, bearing different N-acyl groups has been developed. All compounds of this series are inhibitors of both human O-GlcNAcase and human beta-hexosaminidase, yet some effectively exploit differences between the active site architectures of these two human enzymes which render them selective for O-GlcNAcase. Such inhibitors may be valuable tools in dissecting the role of the O-GlcNAc post-translational modification at the cellular and organismal level since these compounds may have different pharmacokinetic properties when compared to other inhibitors of beta-N-acetyl-glucosaminidases.

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Sperm require β-N-acetylglucosaminidase to penetrate through the egg zona pellucida

Cited by 118 publications

References 42 publications

Fucose, Mannose, and β-N-Acetylglucosamine Glycopolymers Initiate the Mouse Sperm Acrosome Reaction through Convergent Signaling Pathways

Fucose, Mannose, and β-N-Acetylglucosamine Glycopolymers Initiate the Mouse Sperm Acrosome Reaction through Convergent Signaling Pathways

Optimalisation of the Activation Medium and Effect of Inhibiting Activities of Acid Phosphatase, Lactate Dehydrogenase and β-N-Acetylglucosaminidase on the Fertilisation Success of Eurasian Perch (Perca fluviatilis L.)

A divergent synthesis of 2-acyl derivatives of PUGNAc yields selective inhibitors of O-GlcNAcase

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