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Mol Biol Cell January 1, 2018; 29 (26): 3128-3143.

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

Liao Y , Chang HC , Liang FX , Chung PJ , Wei Y , Nguyen TP , Zhou G , Talebian S , Krey LC , Deng FM , Wong TW , Chicote JU , Grifo JA , Keefe DL , Shapiro E , Lepor H , Wu XR , DeSalle R , Garcia-España A , Kim SY , Sun TT .

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.

PubMed ID: 30303751
PMC ID: PMC6340209
Article link: Mol Biol Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cd9 fyn pdcd6ip ski ttn upk1a upk1b upk3a

Article Images: [+] show captions
References [+] :
Adachi, Human uroplakin Ib in ocular surface epithelium. 2000, Pubmed