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

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.

The urothelium: a multi-faceted barrier against a harsh environment

“…In the human bladder, all UPKs are expressed specifically in the urothelium except UPK1B 19 . There is also an increasing appreciation that UPK are expressed in non-urothelial cells 75 – 78 .…”

Toward the understanding of biology of oocyte life cycle in Xenopus Laevis: No oocytes left behind

“…In this connection, it is worth noting that Liao et al reported that uroplakins and a Src‐related tyrosine kinase play conserved roles in fertilization of the mouse and X laevis . Uroplakins are a family of uroplakin proteins (UPs) that consists of two tetraspanins UPIa and UPIb, and three single transmembrane proteins UPII, UPIIIa, and UPIIIb in the mouse and other vertebrates such as cows and frogs .…”

Single-cell analyses of the corneal epithelium: Unique cell types and gene expression profiles

“…4A) revealed that 257 various collagen transcripts were significantly enriched in these cells, with collagen 258 type XVII alpha 1 (col17a1.L) being the most highly expressed marker gene ( Fig Looking at the apical corneal cells (Cluster 3 and 4; Fig. 4A), we detected the expression of larval skin-specific genes (e.g., dan4l.L) (Schreiber and Brown, 2003), goblet cell genes (e.g., itln1) (Dubaissi and Papalopulu, 2011), thyroid hormoneregulated genes (e.g., thdl18.S) (Furlow et al, 1997) and genes mediating signal transduction, as well as membrane permeability and stability (e.g., upk1b.L, atp1b2.L) (Eid and Brandli, 2001;Liao et al, 2018). The gene most uniquely enriched in apical cells encodes otogelin-like 2 (otogl2.L; Fig.…”