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Published 25 November 2002. doi:10.1083/jcb.200204102
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© The Rockefeller University Press, 0021-9525/2002/11/685 $5.00
The Journal of Cell Biology, Volume 159, Number 4, 685-694

Article

Uroplakin IIIb, a urothelial differentiation marker, dimerizes with uroplakin Ib as an early step of urothelial plaque assembly



Fang-Ming Deng1, Feng-Xia Liang1, Liyu Tu2, Katheryn A. Resing6, Ping Hu1, Mark Supino2, Chih-Chi Andrew Hu1,3, Ge Zhou1,3, Mingxiao Ding7, Gert Kreibich2,5 and Tung-Tien Sun1,3,4,5

1 Epithelial Biology Unit, Ronald O. Perelman Department of Dermatology
2 Department of Cell Biology, New York University School of Medicine, New York, NY 10016
3 Department of Pharmacology, New York University School of Medicine, New York, NY 10016
4 Department of Urology, New York University School of Medicine, New York, NY 10016
5 New York University Cancer Institute, New York University School of Medicine, New York, NY 10016
6 Department of Chemistry, University of Colorado, Boulder, CO 80309
7 Department of Cell Biology, College of Life Sciences, Peking University, Beijing, People's Republic of China 100871

Address correspondence to Tung-Tien Sun, Dept. of Dermatology, New York University School of Medicine, 550 First Ave., New York, NY 10016. Tel.: (212) 263-5685. Fax: (212) 263-8561. E-mail: sunt01{at}med.nyu.edu

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.

Key Words: bladder; urothelium; tetraspanin; membrane; DNA mismatch repair enzyme


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