Uroplakin IIIb, a urothelial differentiation marker, dimerizes with uroplakin Ib as an early step of urothelial plaque assembly.
Urothelial plaques consist of four major uroplakins (Ia, Ib, II, and III) that form two-dimensional crystals covering the apical surface of urothelium, and provide unique opportunities for studying membrane protein assembly. Here, we describe a novel 35-kD urothelial plaque-associated glycoprotein that is closely related to uroplakin III: they have a similar overall type 1 transmembrane topology; their amino acid sequences are 34% identical; they share an extracellular juxtamembrane stretch of 19 amino acids; their exit from the ER requires their forming a heterodimer with uroplakin Ib, but not with any other uroplakins; and UPIII-knockout leads to p35 up-regulation, possibly as a compensatory mechanism. Interestingly, p35 contains a stretch of 80 amino acid residues homologous to a hypothetical human DNA mismatch repair enzyme-related protein. Human p35 gene is mapped to chromosome 7q11.23 near the telomeric duplicated region of Williams-Beuren syndrome, a developmental disorder affecting multiple organs including the urinary tract. These results indicate that p35 (uroplakin IIIb) is a urothelial differentiation product structurally and functionally related to uroplakin III, and that p35-UPIb interaction in the ER is an important early step in urothelial plaque assembly.
Deng
Fang-Ming
FM
Epithelial Biology Unit, Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA.
Liang
Feng-Xia
FX
Tu
Liyu
L
Resing
Katheryn A
KA
Hu
Ping
P
Supino
Mark
M
Hu
Chih-Chi Andrew
CC
Zhou
Ge
G
Ding
Mingxiao
M
Kreibich
Gert
G
Sun
Tung-Tien
TT
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers; D002417:Cattle; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D019281:Dimerization; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D059470:Tetraspanins; D014018:Tissue Distribution; D060171:Uroplakin III; D060169:Uroplakin Ib; D019459:Urothelium / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*
D015415:Biomarkers; D008562:Membrane Glycoproteins; D059470:Tetraspanins; C086452:UPK1B protein, human; C554660:UPK3A protein, human; C490124:Upk1b protein, mouse; C554661:Upk3a protein, mouse; C554663:Upk3b protein, mouse; D060171:Uroplakin III; D060169:Uroplakin Ib