Dev105510 1705..1714
نویسندگان
چکیده
In Xenopus laevis, sperm-egg interaction promotes partial proteolysis and/or tyrosine phosphorylation of uroplakin III (UPIII) and the tyrosine kinase Src, which both localize to the cholesterol-enriched egg membrane microdomains (MDs). Here we show that sperm promote proteolysis and/or tyrosine phosphorylation of UPIII and Src in MDs isolated from ovulated and unfertilized eggs (UF-MDs). An antibody against the extracellular domain of UPIII interferes with these events. Inhibition of fertilization by anti-UPIII antibody is rescued by coincubation with UF-MDs. This suggests that, like MDs in intact eggs, the isolated UF-MDs are capable of interacting with sperm, an interaction that does not interfere with normal fertilization but rather augments the ability of sperm to fertilize eggs pretreated with anti-UPIII antibody. This unexpected effect of UF-MDs on sperm requires UPIII function in UF-MDs and protein kinase activity in sperm. MDs isolated from progesterone-treated mature oocytes, but not ovarian immature oocytes, are similarly functional asUF-MDs. Theanti-UPIII extracellular domain antibody binds more effectively to the surface of mature than immatureovarianoocytes.Wepropose that thestructuraland functional competency of the UPIII-Src signaling system in MDs is strictly regulated during oocyte maturation and subsequently in spermmediated egg activation and fertilization. The fertilization-related signaling properties seen in UF-MDs can be partially reconstituted in MDsofhumanembryonickidney293cells (293-MDs) expressingUPIII, Src and uroplakin Ib. However, 293-MDs expressing a proteolysisresistant mutant of UPIII are less functional, suggesting that the availability of UPIII to protease action is important for MD function.
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