Uroplakins play conserved roles in egg fertilization and acquired additional urothelial functions during mammalian divergence

Yi Liao, Hung Chi Chang, Feng Xia Liang, Pei Jung Chung, Yuan Wei, Tuan Phi Nguyen, Ge Zhou, Sheeva Talebian, Lewis C. Krey, Fang Ming Deng, Tak Wah Wong, Javier U. Chicote, James A. Grifo, David L. Keefe, Ellen Shapiro, Herbert Lepor, Xue Ru Wu, Robert DeSalle, Antonio Garcia-España, Sang Yong KimTung Tien Sun

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3128-3143
Number of pages16
JournalMolecular Biology of the Cell
Issue number26
Publication statusPublished - 2018 Dec 15

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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