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In oocytes, uroplakins colocalize with CD9 on cell-surface and multivesicular body-derived exosomes, and the cytoplasmic tail of UPIIIa undergoes a conserved fertilization-dependent, Fyn-mediated tyrosine phosphorylation that also occurs in Xenopus laevis eggs. Uroplakin knockout and antibody blocking reduce mouse eggs\u2019 fertilization rate in in vitro fertilization assays, and UPII\/IIIa double-knockout mice have a smaller litter size. Phylogenetic analyses showed that uroplakin sequences underwent significant mammal-specific changes. These results suggest that, by mediating signal transduction and modulating membrane stability that do not require two-dimensional-crystal formation, uroplakins can perform conserved and more ancestral fertilization functions in mouse and frog eggs. Uroplakins acquired the ability to form two-dimensional-crystalline plaques during mammalian divergence, enabling them to perform additional functions, including umbrella cell enlargement and the formation of permeability and mechanical barriers, to protect\/modify the apical surface of the modern-day mammalian urothelium.<\/jats:p>","DOI":"10.1091\/mbc.e18-08-0496","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T12:06:40Z","timestamp":1539173200000},"page":"3128-3143","source":"Crossref","is-referenced-by-count":11,"title":["Uroplakins play conserved roles in egg fertilization and acquired additional urothelial functions during mammalian divergence"],"prefix":"10.1091","volume":"29","author":[{"given":"Yi","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Cell Biology, New York University School of Medicine, New York, NY 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