Disease relevance of ZP3

• Mouse lines lacking either ZP1 or ZP3 have been established with abnormal or absent zona matrices and varying degrees of infertility to examine zona structure and function in vivo [1].
• In contrast to hZPC, the acrosome reaction induced by recombinant hZPB was not inhibited by pertussis toxin [2].
• To facilitate our understanding of the role of zona pellucida glycoproteins during fertilization in humans, recombinant human zona pellucida glycoprotein-A (hZPA), -B (hZPB) and -C (hZPC) were obtained by using Escherichia coli and baculovirus expression systems [2].
• ZP2 and ZP3 Traffic Independently within Oocytes prior to Assembly into the Extracellular Zona Pellucida [3].
• Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida [4].

High impact information on ZP3

• These receptors include the receptor tyrosine kinases that mediate the actions of growth factors such as epidermal growth factor, insulin, insulin-like growth factor as well as receptors for atrial natiuretic hormone or the zona pellucida protein (ZP3) and integrins [5].
• A 95-kilodalton mouse sperm protein with characteristics of a protein tyrosine kinase has been identified as a receptor for ZP3, a glycoprotein in the egg's extracellular matrix [6].
• Antibodies against a synthetic peptide from the intracellular domain recognized a 95-kilodalton human sperm protein that contains phosphotyrosine; human ZP3 stimulates the kinase activity of this sperm protein [6].
• Our results demonstrate that the C-terminal transmembrane domain and short cytoplasmic tail of ZP2 and ZP3 are not required for secretion, but are essential for assembly [7].
• The primacy of the T cell response in the pathogenesis of disease is further substantiated by defining oophoritogenic peptides as small as eight amino acids (Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln) that do not elicit an antibody response to the full-length ZP3 peptide [4].

Chemical compound and disease context of ZP3

• However, only a few of these knockout of genes such as encoding oocyte glycoprotein coat comprised of zona pellucida (ZP) 1, ZP2 and ZP3 and oocute plasma membrane specific proteins showed a specific and exclusive target infertility effect without concomitant effects on the non-reproductive organ system [8].

Biological context of ZP3

• The amino acid sequence derived from the cDNA sequence shares high sequence homologies to mouse (90%), hamster (78%), and human (65%) ZP3 (ZPC) glycoproteins, indicating that the rat and mouse ZP3 have quite a conserved amino acid sequence, including the potential glycosylation sites [9].
• All treatments altered the SDS-PAGE migration of recombinant hZP3, concordant with cleavage by a furin family member and Golgi glycosylation of secreted hZP3 [10].
• The 3' end of the POM-ZP3 transcript is 99% identical to ZP3 and appears to have arisen from a duplication of the last four exons (exons 5-8) of ZP3 [11].
• By fluorescence in situ hybridization, genomic fragments of ZP3 and a human homologue of POM121 were localized to chromosome 7q11.23 [11].
• Acrosome-intact sperm recognize and bind to O-linked oligosaccharides linked to Ser residues at the sperm combining-site of ZP3 [12].

Anatomical context of ZP3

• In mice and humans, this matrix is known as the zona pellucida and comprises three glycoproteins: ZP1, ZP2 and ZP3 [1].
• Mass spectrometry analysis of recombinant human ZP3 expressed in glycosylation-deficient CHO cells [13].
• ZP3 is the ligand for primary sperm binding and important for the induction of the acrosome reaction [14].
• Human ZP3 expressed in mouse oocytes had an apparent mass (64 kDa) indistinguishable from native human ZP3 and distinct from mouse ZP3 (83 kDa) [15].
• Under reducing conditions, zonae from unfertilized eggs separated into three acidic proteins with molecular weight ranges of 90,000-110,000 (ZP1), 64,000-78,000 (ZP2) and 57,000-73,000 (ZP3) [16].

Associations of ZP3 with chemical compounds

• Previous studies have suggested that the sperm receptor activity of the zona pellucida resides in specific oligosaccharide chains on the ZP3 glycoprotein [17].
• These results support the model that initial interaction of the fertilizing spermatozoon with ZP3 involves the tyrosine phosphorylation of a 95 kDa tyrosine kinase protein and that this requires capacitation [18].
• Multivalent oligosaccharides on ZP3, as well as synthetic polymers terminating in N-acetylglucosamine aggregate GalT, leading to activation of a heterotrimeric G protein cascade and culminating in the acrosome reaction [19].
• Possum ZP3 has a 46% amino acid identity with eutherian ZP3 and shares similar structural characteristics including 12 conserved cysteine residues, N-linked glycosylation sites and hydrophobic regions [20].
• Conserved ZPC domains and motifs present in the Xenopus sequence included a signal peptide sequence, an N-linked glycosylation site, and 12 aligned Cys residues [21].

Regulatory relationships of ZP3

• DNA from the blood of 120 men and women and from 38 single lymphocytes was amplified by polymerase chain reaction (PCR) with the SRY and control (ZP3) gene primers [22].
• Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice [23].

Other interactions of ZP3

• By using the polymerase chain reaction, a full-length cDNA of human ZP3 was isolated from human ovarian poly(A)+ RNA and used to deduce the structure of human ZP3 mRNA [24].
• Taken together, these data suggest that partial duplications of human ZP3 and a POM121-like gene have resulted in a fusion transcript, POM-ZP3, that is expressed in multiple human tissues [11].
• Recently, the hamster sperm receptor, a 56,000 Mr zona pellucida glycoprotein called hZP3, was identified and partially characterized (C. C. Moller et al., (1990). Dev. Biol. 137, 276-286) [25].
• The ZP3 aa sequence similarities were examined using the GAP program (GCG) [26].
• 11 (58%) of the embryos were judged to be "male" and 8 (42%) "female". The SRY and ZP3 gene primers selected are highly specific and give accurate results in sex determination and their use provides a new reliable method for routine preimplantation and general prenatal sex determination in man [22].

Analytical, diagnostic and therapeutic context of ZP3

• Southern blotting, gene cloning, and sequence analysis were used to show that ZP3 is not a single-copy gene and that the human genome contains a second polymorphic locus which, due to an extra G residue in exon 8, has the potential to encode a truncated protein of 372 amino acids [27].
• ZP3 material was also detected in cumulus cells by immunohistochemistry [28].
• Southern blot analysis of genomic DNA and gene-cloning experiments have recently shown that the human ZP3 gene is not a single-copy gene [29].
• Comparison of ZP3 protein sequences among vertebrate species: to obtain a consensus sequence for immunocontraception [26].
• These results clearly show the presence of ZP3 on primordial follicles and in granulosa cells, and this could explain the ZP-induced ovarian pathology after active immunization with ZP3 [30].

References