Aktivierung und Freisetzung von Ovastacin bei der Befruchtung des Säugereies, sowie Studien zur Lokalisation und Phylogenie
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Westphal, Hagen
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Abstract
The zinc-dependent astacin-metalloproteinase ovastacin is released in the course of the cortical reaction upon fertilization of the mammalian ovum. Once released ovastacin cleaves the Zona pellucida protein 2 (ZP2) which leads to the hardening of the Zona pellucida. On one hand this prevents the penetration by additional spermatozoa, on the other hand the hardened Zona is protecting the early embryo until implantation. The ovastacin-deciency reduces the fecundity in mice signicantly. A deficiency of its endogenous inhibitor Fetuin-B leads to female infertility. Thus ovastacin plays a crucial role in the proteolytic web of fertilization.
There were no data available concerning the in vivo activation of ovastacin at the start of this project. Furthermore there was no function of its C-terminal domain published. The expression was published as oocyte-specific.
During this doctoral thesis I was able to reveal that ovastacin is already activated intracellulary and does not have to be cleaved upon release by a serine protease like other members of the astacin family of metalloproteineases. Furthermore a partial prefertilization cleavage of the Zona pellucida by ovastacin was confirmed.
In this context the results demonstrated a retention of the C-terminal domain at the surface of the plasmalemma of the zygote. This supports a published receptor function of this enzyme.
The previously described oocyte-specific expression was extended by the thymus.
In silico analysis regarding the phylogeny of ovastacin suggests the evolution of ovastacin from an amniotic hatching enzyme during the first appearance of the eutheria.