Uroplakins (UP (UPIa, UPIb, UPII, UPIIIa))

Uroplakins are a family of four major integral membrane proteins (UPIa, UPIb, UPII, UPIIIa) highly expressed in mammalian urothelium, where they assemble into two heterodimers (UPIa/II and UPIb/IIIa) that form heterotetramers and hexagonally packed 16-nm particles creating rigid two-dimensional crystalline urothelial plaques on the apical surface of umbrella cells.[1][3] These plaques cover the urothelial surface, enabling umbrella cell enlargement, a highly efficient permeability barrier against urine, and mechanical protection for the bladder epithelium.[1][3][4] UPIa and UPIb belong to the tetraspanin family, while UPII and UPIIIa are single-span proteins; their assembly occurs progressively in the ER, Golgi, and trans-Golgi network, involving glycosylation and furin cleavage.[3] Beyond urothelium, uroplakins express in non-urothelial sites like oocytes, sperm, and other urogenital tissues, mediating conserved roles in egg fertilization via signal transduction, Fyn-mediated tyrosine phosphorylation, and colocalization with CD9 on exosomes, without requiring plaque formation.[1] Knockout studies in mice reveal defects in urothelial barrier function, umbrella cell expansion, and reduced fertilization rates, highlighting their essential roles.[1][3] Pathologically, uroplakins facilitate uropathogenic E. coli attachment in urinary tract infections and serve as markers in urothelial biology, with genetic ablation linked to vesicoureteral reflux and hydronephrosis.[1][3] No drugs directly target uroplakins therapeutically, though their tissue specificity suggests potential in bladder disorders.[2][3][5]

Other names

Uroplakin-1a (UP1a, UPK1A)Uroplakin-1b (UP1b, UPK1B)Uroplakin-2 (UP2, UPII, UPK2)Uroplakin-3a (UP3a, UPIIIa, UPK3A)Uroplakin-3b (UP3b, UPIIIb, UPK3B)