Molecular cloning of a 47 kDa tissue-specific and differentiation-dependent urothelial cell surface glycoprotein.
Despite the fact that bladder epithelium has many interesting biological features and is a frequent site of carcinoma formation, relatively little is known about its biochemical differentiation. We have shown recently that a 47 kDa glycoprotein, uroplakin III (UPIII), in conjunction with uroplakins I (27 kDa) and II (15 kDa), forms the asymmetric unit membrane (AUM)--a highly specialized biomembrane characteristic of the apical surface of bladder epithelium. Deglycosylation and cDNA sequencing revealed that UPIII contains up to 20 kDa of N-linked sugars attached to a core protein of 28.9 kDa. The presence of an N-terminal signal peptide sequence and a single transmembrane domain located near the C terminus, plus the N-terminal location of all the potential N-glycosylation sites, points to a type I (N-exo/C-cyto) configuration. Thus the mass of the extracellular domain (20 kDa plus up to 20 kDa of sugar) of UPIII greatly exceeds that of its intracellular domain (5 kDa). Such an asymmetrical mass distribution, a feature shared by the other two major uroplakins, provides a molecular explanation as to why the luminal leaflet of AUM is almost twice as thick as the cytoplasmic one. The fact that of the three major proteins of AUM only UPIII has a significant cytoplasmic domain suggests that this molecule may play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells.
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Ronald O. Perelman Department of Dermatology, New York University School of Medicine, NY 10016.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002454:Cell Differentiation; D002462:Cell Membrane / Q000648:ultrastructure; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics; D004848:Epithelium / Q000737:chemistry / Q000648:ultrastructure; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009928:Organ Specificity; D021382:Protein Sorting Signals / Q000235:genetics; D001743:Urinary Bladder / Q000737:chemistry*; D060171:Uroplakin III
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D060171:Uroplakin III