1. Uroplakins play conserved roles in egg fertilization and acquired additional urothelial functions during mammalian divergence
- Author
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Lewis Krey, S. Talebian, Tuan Phi Nguyen, Herbert Lepor, Tung-Tien Sun, H.C. Chang, Feng-Xia Liang, Pei Jung Chung, Ge Zhou, Xue-Ru Wu, Yuan Wei, James A. Grifo, Antonio Garcia-España, Robert DeSalle, Sang Yong Kim, Tak Wah Wong, Fang Ming Deng, David L. Keefe, Ellen Shapiro, Javier U. Chicote, and Yi Liao
- Subjects
Male ,0301 basic medicine ,Cell type ,Litter Size ,Genetic Speciation ,Zygote ,Cellular differentiation ,Parthenogenesis ,Xenopus ,Biology ,Proto-Oncogene Proteins c-fyn ,urologic and male genital diseases ,Tetraspanin 29 ,Mice ,Xenopus laevis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Testis ,Uroplakins ,Animals ,Phosphorylation ,Urothelium ,Molecular Biology ,Phylogeny ,Mice, Knockout ,Ovary ,Cell Differentiation ,Tyrosine phosphorylation ,Articles ,Cell Biology ,biology.organism_classification ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Membrane Trafficking ,Cytoplasm ,Fertilization ,030220 oncology & carcinogenesis ,Oocytes ,Female ,Signal transduction ,Signal Transduction - Abstract
Uroplakin (UP) tetraspanins and their associated proteins are major mammalian urothelial differentiation products that form unique two-dimensional crystals of 16-nm particles (“urothelial plaques”) covering the apical urothelial surface. Although uroplakins are highly expressed only in mammalian urothelium and are often referred to as being urothelium specific, they are also expressed in several mouse nonurothelial cell types in stomach, kidney, prostate, epididymis, testis/sperms, and ovary/oocytes. 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’ 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.
- Published
- 2018