Features that affect secretion and assembly of zona pellucida glycoproteins during mammalian oogenesis.

Luca Jovine, Huayu Qi, Zev Williams, Eveline S. Litscher, Paul M. Wassarman

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


For sperm to fertilize eggs, they must bind to and penetrate the zona pellucida (ZP) that surrounds the plasma membrane of all mammalian eggs. The ZP first appears during oocyte growth and increases in thickness as oocytes increase in diameter. The ZP is an extracellular matrix composed of long, crosslinked filaments. In mice, three glycoproteins, called mZP1-3, are synthesised and secreted by growing oocytes and assembled into a thick (-6.5 microm) extracellular coat over a 2-3 week period. Recently, we identified several regions of nascent ZP glycoproteins that affect their secretion and incorporation into the ZP (assembly) by growing oocytes. Among these are the ZP domain, the consensus furin cleavage site (CFCS) and the C-terminal propeptide (CTP) with its transmembrane domain (TMD), external hydrophobic patch (EHP), charged patch (CP), conserved cysteine (Cys) residue, and short cytoplasmic tail (CT). Particularly important is the ZP domain, a approximately 260 amino acid region with 8 conserved Cys residues that is common to a variety of extracellular proteins of diverse functions found in a wide range of multicellular eukaryotes. Our results show that the ZP domain functions as a polymerisation module and that its N-terminal half, including 4 conserved Cys residues, is largely responsible for this role. Additionally, two conserved hydrophobic sequences, one within the ZP domain (internal hydrophobic patch; IHP) and another within the CTP (EHP), apparently regulate polymerisation of nascent ZP glycoproteins. Collectively, our findings suggest a general mechanism for assembly of all ZP domain proteins based on coupling between proteolytic processing and polymerisation.

Original languageEnglish (US)
Pages (from-to)187-201
Number of pages15
JournalSociety of Reproduction and Fertility supplement
StatePublished - 2007
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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