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A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice
Monospermic fertilization is mediated by the extracellular zona pellucida composed of ZP1, ZP2 and ZP3. Sperm bind to the N-terminus of ZP2 which is cleaved after fertilization by ovastacin (encoded by Astl) exocytosed from egg cortical granules to prevent sperm binding. Astl(Null) mice lack the pos...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293279/ https://www.ncbi.nlm.nih.gov/pubmed/28114310 http://dx.doi.org/10.1371/journal.pgen.1006580 |
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author | Xiong, Bo Zhao, Yangu Beall, Stephanie Sadusky, Anna Burkart Dean, Jurrien |
author_facet | Xiong, Bo Zhao, Yangu Beall, Stephanie Sadusky, Anna Burkart Dean, Jurrien |
author_sort | Xiong, Bo |
collection | PubMed |
description | Monospermic fertilization is mediated by the extracellular zona pellucida composed of ZP1, ZP2 and ZP3. Sperm bind to the N-terminus of ZP2 which is cleaved after fertilization by ovastacin (encoded by Astl) exocytosed from egg cortical granules to prevent sperm binding. Astl(Null) mice lack the post-fertilization block to sperm binding and the ability to rescue this phenotype with Astl(mCherry) transgenic mice confirms the role of ovastacin in providing a definitive block to polyspermy. During oogenesis, endogenous ovastacin traffics through the endomembrane system prior to storage in peripherally located cortical granules. Deletion mutants of ovastacin(mCherry) expressed in growing oocytes define a unique 7 amino acid motif near its N-terminus that is necessary and sufficient for cortical granule localization. Deletion of the 7 amino acids by CRISPR/Cas9 at the endogenous locus (Astl(Δ)) prevents cortical granule localization of ovastacin. The misdirected enzyme is present within the endomembrane system and ZP2 is prematurely cleaved. Sperm bind poorly to the zona pellucida of Astl(Δ/Δ) mice with partially cleaved ZP2 and female mice are sub-fertile. |
format | Online Article Text |
id | pubmed-5293279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52932792017-02-17 A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice Xiong, Bo Zhao, Yangu Beall, Stephanie Sadusky, Anna Burkart Dean, Jurrien PLoS Genet Research Article Monospermic fertilization is mediated by the extracellular zona pellucida composed of ZP1, ZP2 and ZP3. Sperm bind to the N-terminus of ZP2 which is cleaved after fertilization by ovastacin (encoded by Astl) exocytosed from egg cortical granules to prevent sperm binding. Astl(Null) mice lack the post-fertilization block to sperm binding and the ability to rescue this phenotype with Astl(mCherry) transgenic mice confirms the role of ovastacin in providing a definitive block to polyspermy. During oogenesis, endogenous ovastacin traffics through the endomembrane system prior to storage in peripherally located cortical granules. Deletion mutants of ovastacin(mCherry) expressed in growing oocytes define a unique 7 amino acid motif near its N-terminus that is necessary and sufficient for cortical granule localization. Deletion of the 7 amino acids by CRISPR/Cas9 at the endogenous locus (Astl(Δ)) prevents cortical granule localization of ovastacin. The misdirected enzyme is present within the endomembrane system and ZP2 is prematurely cleaved. Sperm bind poorly to the zona pellucida of Astl(Δ/Δ) mice with partially cleaved ZP2 and female mice are sub-fertile. Public Library of Science 2017-01-23 /pmc/articles/PMC5293279/ /pubmed/28114310 http://dx.doi.org/10.1371/journal.pgen.1006580 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Xiong, Bo Zhao, Yangu Beall, Stephanie Sadusky, Anna Burkart Dean, Jurrien A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice |
title | A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice |
title_full | A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice |
title_fullStr | A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice |
title_full_unstemmed | A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice |
title_short | A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice |
title_sort | unique egg cortical granule localization motif is required for ovastacin sequestration to prevent premature zp2 cleavage and ensure female fertility in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293279/ https://www.ncbi.nlm.nih.gov/pubmed/28114310 http://dx.doi.org/10.1371/journal.pgen.1006580 |
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