NYU Langone Medical Center

Bladder Epithelium

Keith Porter, a pioneer of modern cell biology, discovered in the early 60’s that numerous rigid-looking plaques cover the entire apical surface of mammalian bladder epithelium. Later investigators found that these plaques consist of 2D crystals of hexagonally arranged 16-nm particles protruding luminally, hence the term “asymmetric unit membrane” (AUM). This structure attracted the attention of several well-known investigators including Andrew Staehelin, David Robertson and Marian Hicks, who studied the ultrastructure of AUM in the 70’s and 80’s. Although these investigators succeeded in partially purifying the AUM’s, studies on AUM protein subunits were hindered by the fact that no one was able to generate monospecific antibodies to the several putative AUM subunits. Without even a basic understanding of the protein composition of AUM, the field practically died in the late 80’s. Since 1988 when we entered into this area, we have identified and characterized several novel AUM subunits that we named uroplakins (urothelial plaque-associated proteins). Although this is still a relatively young field, our studies have established that uroplakins are useful markers for metastatic bladder cancer; that uroplakin Ia may serve as the urothelial receptor for the uropathogenic E. coli that causes >90% of urinary tract infections; that urinary bladder can be converted into a novel bladder bioreactor; that one canuse uroplakin promoter to generate a panel of transgenic mouse models for dissecting the molecular pathways of bladder tumorigenesis; and that uroplakin defects may lead to a number of important urinary tract defects.

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