Assembly of urothelial plaques: tetraspanin function in membrane protein trafficking

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 ma...

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Bibliographic Details
Published in:Molecular biology of the cell 2005-09, Vol.16 (9), p.3937-3950
Main Authors: Hu, Chih-Chi Andrew, Liang, Feng-Xia, Zhou, Ge, Tu, Liyu, Tang, Chih-Hang Anthony, Zhou, Jessica, Kreibich, Gert, Sun, Tung-Tien
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies, Monoclonal
Cattle
Cell Differentiation - physiology
Cells, Cultured
Dimerization
Glycosylation
Membrane Glycoproteins - metabolism
Membrane Proteins - immunology
Membrane Proteins - metabolism
Membrane Proteins - physiology
Molecular Sequence Data
Protein Precursors - immunology
Protein Precursors - metabolism
Protein Transport - physiology
Uroplakin II
Uroplakin III
Urothelium - cytology
Urothelium - metabolism
Urothelium - physiology
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E05-02-0136