A single domain of the ZP2 zona pellucida protein mediates gamete recognition in mice and humans

Avella, Matteo A.; Baibakov, Boris; Dean, Jurrien

doi:10.1083/jcb.201404025

Cited by 145 publications

(182 citation statements)

References 43 publications

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“…Initially, ZP2, a major component of the ZP matrix, was proposed to serve as a ligand for secondary sperm binding (for acrosome-reacted spermatozoa) to the surface of the ZP. Recent work using mouse oocytes expressing "humanized" zona proteins by replacing mouse ZP1-3 with human ZP1-4 clearly showed that ZP2 but not ZP3 is necessary and sufficient for binding and penetration of human spermatozoa to the humanized ZP matrix (Avella et al 2014). Thus, the same pair of molecules might keep working through the entire process, from initial contact until final penetration of the ZP.…”

Section: Penetration Of the Zpmentioning

confidence: 97%

“…Nonetheless, IVF is still a promising approach for discovering new molecular models for sperm-ZP interactions (Visconti and Florman 2010;Redgrove et al 2012;Nagdas et al 2015). A recent study using gene rescue experiments clearly demonstrated that human spermatozoa could recognize the human zona pellucida protein ZP2 (Avella et al 2014). The N-terminal domains (spanning amino acid residues 39-154 or 39-267) of human ZP2 exhibited high affinity for spermatozoa and enabled sperm binding to the ZP matrix.…”

Section: Adhesion To the Zpmentioning

confidence: 98%

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Site of Mammalian Sperm Acrosome Reaction

Hirohashi

2016

Sperm Acrosome Biogenesis and Function During Fertilization

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Until recently, no special attention has been paid to the question of the site of mammalian sperm acrosome reaction (AR) in the female reproductive tract. Because AR is an essential process that enables the spermatozoon to fertilize, it is generally believed that it occurs at a specific step during sperm-egg interaction. It is generally thought that "the site of action coincides with the site of commitment." Thus, understanding the roles of AR and acrosomal substances is needed to gain insight into the site of the sperm commitment to undergo AR.

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Section: Penetration Of the Zpmentioning

confidence: 97%

Section: Adhesion To the Zpmentioning

confidence: 98%

Site of Mammalian Sperm Acrosome Reaction

Hirohashi

2016

Sperm Acrosome Biogenesis and Function During Fertilization

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“…We cloned rat IE3, a monoclonal antibody that binds the amino terminus of mouse ZP2, a critical ligand for taxon-specifi c sperm binding [8] ( Figure S2A). IE3 transiently inhibits female mouse fertility when introduced as ascites fl uid through intraperitoneal injection [9].…”

Section: Magazinementioning

confidence: 99%

Vectored antibody gene delivery mediates long-term contraception

Olvera

Akbari

et al. 2015

Current Biology

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Development of non-surgical methods of long-term or permanent contraception remains a challenge. Towards this objective, we show that intramuscular injection of a replication-incompetent, recombinant adeno-associated virus (rAAV) designed to express an antibody that binds gonadotropin-releasing hormone (GnRH), a master regulator of reproduction in vertebrates, results in long-term infertility in male and female mice. Female mice are also rendered infertile through rAAV-dependent expression of an antibody that binds to the zona pellucida (ZP), a glycoprotein matrix that surrounds the egg and functions as a sperm-binding site. Many proteins known or suspected to be important for reproduction can be targeted, potentially reversibly, using this approach, which we refer to as vectored contraception (VC).

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“…The HISRainbow construct was generated by sequentially ligating lox 2272+lox N+lox P, polyA×3+lox 2272, H3.3-eGFP, polyA+lox N, H3.3 R26K -eCFP, polyA+lox P, H3.3 K27R -mCherry, polyA+frt (all with 5′ XbaI restriction sites and 3′ NheI or EcoRI restriction sites) into the pCAGEN plasmid (Addgene) (Rinkevich et al, 2011). After digestion with SpeI and EcoRI, the transgene was gelpurified and injected into the male pronucleus (Avella et al, 2014). These mice were then crossed with Flpe-Cre transgenic mice (Jackson Laboratory) for several generations until only one copy of transgene was detected in the mouse line.…”

Section: Micementioning

confidence: 99%

Genetic mosaics and time-lapse imaging identify functions of histone H3.3 residues in mouse oocytes and embryos

et al. 2017

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During development from oocyte to embryo, genetic programs in mouse germ cells are reshaped by chromatin remodeling to orchestrate the onset of development. Epigenetic modifications of specific amino acid residues of core histones and their isoforms can dramatically alter activation and suppression of gene expression. H3.3 is a histone H3 variant that plays essential roles in mouse oocytes and early embryos, but the functional role of individual amino acid residues has been unclear because of technical hurdles. Here, we describe two strategies that successfully investigated the functions of three individual H3.3 residues in oogenesis, cleavagestage embryogenesis and early development. We first generated genetic mosaic ovaries and blastocysts with stochastic expression of wild-type or mutant H3.3 alleles and showed dominant negative effects of H3.3R26 and H3.3K27 in modulating oogenesis and partitioning cells to the inner cell mass of the early embryo. Timelapse imaging assays also revealed the essential roles of H3.3K56 in efficient H2B incorporation and paternal pronuclei formation. Application of these strategies can be extended to investigate roles of additional H3.3 residues and has implications for use in other developmental systems.

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A single domain of the ZP2 zona pellucida protein mediates gamete recognition in mice and humans

Abstract: The ZP251–149 domain is necessary for human and mouse gamete recognition on the surface of the zona pellucida and for mouse fertility.

Cited by 145 publications

References 43 publications

Site of Mammalian Sperm Acrosome Reaction

Site of Mammalian Sperm Acrosome Reaction

Vectored antibody gene delivery mediates long-term contraception

Genetic mosaics and time-lapse imaging identify functions of histone H3.3 residues in mouse oocytes and embryos

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