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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 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 fascinated and 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 most of the 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 uroplakin is still a relatively new field, our studies on these
proteins 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 which causes >90% of urinary tract infections; that
urinary bladder can be converted into a novel bladder bioreactor; that one can
use uroplakin promoter to generate a panel of transgenic models for dissecting
the molecular pathways of bladder tumorigenesis; and that uroplakin defects may
lead to a number of important urinary tract defects. |
