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Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis

[Image: see text] As a prerequisite to mammalian fertilization, the sperm acrosomal vesicle fuses with the plasma membrane and the acrosome contents are exocytosed. Induction occurs through engagement of the sperm receptors by multiple sugar residues. Multivalent polymers displaying mannose, fucose,...

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Autores principales: Huang, He, Rodolis, Maria T., Bhatia, Surita R., Sampson, Nicole S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464008/
https://www.ncbi.nlm.nih.gov/pubmed/28509550
http://dx.doi.org/10.1021/acs.biochem.7b00166
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author Huang, He
Rodolis, Maria T.
Bhatia, Surita R.
Sampson, Nicole S.
author_facet Huang, He
Rodolis, Maria T.
Bhatia, Surita R.
Sampson, Nicole S.
author_sort Huang, He
collection PubMed
description [Image: see text] As a prerequisite to mammalian fertilization, the sperm acrosomal vesicle fuses with the plasma membrane and the acrosome contents are exocytosed. Induction occurs through engagement of the sperm receptors by multiple sugar residues. Multivalent polymers displaying mannose, fucose, or GlcNAc are effective synthetic inducers of mouse sperm acrosomal exocytosis (AE). Each carbohydrate is proposed to have a distinct binding site on the sperm cell surface. To determine the role of the scaffold structure in the efficiency of AE induction, different polymer backbones were employed to display the different activating sugar residues. These glycopolymers were prepared by ruthenium-catalyzed ring-opening metathesis of 5-substituted norbornene or cyclooctene. The conformations of the glycopolymers were characterized by small-angle X-ray scattering. Polynorbornene displaying mannose, fucose, or GlcNAc forms flexible cylinders in aqueous solution. However, polycyclooctenes displaying any of these same sugars are much more flexible and form random coils. The flexible polycyclooctenes displaying fucose or GlcNAc were less effective inducers of AE than their norbornene counterparts. In contrast, polycyclooctene displaying mannose was the most effective AE inducer and had a more collapsed spherelike structure. Our results suggest that the AE efficacy of fucose, GlcNAc, and mannose polymers relies on a relatively rigid polymer that can stabilize receptor signaling complexes.
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spelling pubmed-54640082018-05-16 Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis Huang, He Rodolis, Maria T. Bhatia, Surita R. Sampson, Nicole S. Biochemistry [Image: see text] As a prerequisite to mammalian fertilization, the sperm acrosomal vesicle fuses with the plasma membrane and the acrosome contents are exocytosed. Induction occurs through engagement of the sperm receptors by multiple sugar residues. Multivalent polymers displaying mannose, fucose, or GlcNAc are effective synthetic inducers of mouse sperm acrosomal exocytosis (AE). Each carbohydrate is proposed to have a distinct binding site on the sperm cell surface. To determine the role of the scaffold structure in the efficiency of AE induction, different polymer backbones were employed to display the different activating sugar residues. These glycopolymers were prepared by ruthenium-catalyzed ring-opening metathesis of 5-substituted norbornene or cyclooctene. The conformations of the glycopolymers were characterized by small-angle X-ray scattering. Polynorbornene displaying mannose, fucose, or GlcNAc forms flexible cylinders in aqueous solution. However, polycyclooctenes displaying any of these same sugars are much more flexible and form random coils. The flexible polycyclooctenes displaying fucose or GlcNAc were less effective inducers of AE than their norbornene counterparts. In contrast, polycyclooctene displaying mannose was the most effective AE inducer and had a more collapsed spherelike structure. Our results suggest that the AE efficacy of fucose, GlcNAc, and mannose polymers relies on a relatively rigid polymer that can stabilize receptor signaling complexes. American Chemical Society 2017-05-16 2017-06-06 /pmc/articles/PMC5464008/ /pubmed/28509550 http://dx.doi.org/10.1021/acs.biochem.7b00166 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Huang, He
Rodolis, Maria T.
Bhatia, Surita R.
Sampson, Nicole S.
Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis
title Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis
title_full Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis
title_fullStr Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis
title_full_unstemmed Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis
title_short Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis
title_sort sugars require rigid multivalent displays for activation of mouse sperm acrosomal exocytosis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464008/
https://www.ncbi.nlm.nih.gov/pubmed/28509550
http://dx.doi.org/10.1021/acs.biochem.7b00166
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