Mouse zona pellucida genes and glycoproteins.
The zona pellucida (ZP) is a thick extracellular coat that surrounds all mammalian eggs. The ZP plays important roles during oogenesis, fertilization, and preimplantation development. The mouse ZP consists of only three glycoproteins, called ZP1, ZP2, and ZP3. All three glycoproteins are essential structural components of the ZP. Additionally, ZP3 serves as a primary sperm receptor and acrosome reaction-inducer, and ZP2 serves as a secondary sperm receptor during fertilization. ZP1, ZP2, and ZP3 are encoded by single-copy genes present on three different chromosomes. The genes are expressed exclusively by mouse oocytes as they grow and the cellular specificity can be ascribed to cis-acting sequences close to the site of transcription initiation and to certain trans-acting factors. Concomitantly, ZP polypeptides are synthesized, modified with N- and O-linked oligosaccharides, secreted, and assembled into crosslinked filaments that exhibit a structural repeat. Nascent ZP glycoproteins are incorporated into large secretory vesicles that fuse with the oocyte plasma membrane and deposit nascent ZP glycoproteins into the innermost layer of the thickening ZP. Each ZP polypeptide possesses several characteristic features, including an N-terminal signal sequence, a ZP domain, a consensus furin cleavage site, and a C-terminal transmembrane domain. The latter is required for assembly of nascent ZP polypeptides into a ZP, cleavage at the consensus furin cleavage site is required for secretion, and the ZP domain supports protein:protein interactions during ZP assembly. At ovulation, when meiotic maturation of oocytes occurs and chromosomes condense into bivalents, expression of the three ZP genes ceases. Using "knockout mice", in the absence of either ZP2 or ZP3 expression, a ZP fails to assemble around growing oocytes and females are infertile. There is no effect on males. In the absence of ZP1 expression, a disorganized ZP assembles around growing oocytes and females exhibit reduced fertility. These observations are consistent with the current model for ZP structure in which ZP2 and ZP3 form long Z filaments crosslinked by ZP1.
Wassarman
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Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. paul.wassarman@mssm.edu
Jovine
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Litscher
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D000818:Animals; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051379:Mice; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015044:Zona Pellucida; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; C000606519:Zp1 protein, mouse; C000606520:Zp2 protein, mouse; C000606521:Zp3 protein, mouse