Assembly of urothelial plaques: Tetraspanin function in membrane protein trafficking

Chih Chi Andrew Hu, Feng Xia Liang, Ge Zhou, Liyu Tu, Chih Hang Anthony Tang, Jessica Zhou, Gert Kreibich, Tung Tien Sun

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


The apical surface of mammalian urothelium is covered by 16-nm protein particles packed hexagonally to form 2D crystals of asymmetric unit membranes (AUM) that contribute to the remarkable permeability barrier function of the urinary bladder. We have shown previously that bovine AUMs contain four major integral membrane proteins, i.e., uroplakins Ia, Ib, II, and IIIa, and that UPIa and Ib (both tetraspanins) form heterodimers with UPII and IIIa, respectively. Using a panel of antibodies recognizing different conformational states of uroplakins, we demonstrate that the UPIa-dependent, furin-mediated cleavage of the prosequence of UPII leads to global conformational changes in mature UPII and that UPIb also induces conformational changes in its partner UPIIIa. We further demonstrate that tetraspanins CD9, CD81, and CD82 can stabilize their partner protein CD4. These results indicate that tetraspanin uroplakins, and some other tetraspanin proteins, can induce conformational changes leading to the ER-exit, stabilization, and cell surface expression of their associated, single-transmembrane-domained partner proteins and thus can function as "maturation-facilitators." We propose a model of AUM assembly in which conformational changes in integral membrane proteins induced by uroplakin interactions, differentiation-dependent glycosylation, and the removal of the prosequence of UPII play roles in regulating the assembly of uroplakins to form AUM.

Original languageEnglish (US)
Pages (from-to)3937-3950
Number of pages14
JournalMolecular Biology of the Cell
Issue number9
StatePublished - Sep 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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