and Jürgen Roth2
Medical University of Vienna, Vienna, Austria
University of Zurich, Zurich, Switzerland
Umbrella Cell: Surface Specializations
The wall of the urinary passages, including the surfaces of the renal pelvis, the ureters, the urinary bladder, and proximal parts of the urethra, is covered by a unique specialized epithelium, the transitional epithelium or urothelium. The urothelium is stratified and composed of three types of cells: basal precursor cells, intermediate cells, and large superficial umbrella cells. The latter line the lumina of the organs and are responsible for the main specific urothelial functions. Results indicate that in the adult bladder after injury, intermediate cells function as progenitors for superficial cells. The urothelium enables the retention of urine and forms a barrier that makes it impermeable to water and movement of ions and metabolites. The various types of superficial cells in the distinctive parts of the urinary tract epithelium differ considerably in the expression of uroplakins, cytokeratins, and in the structure of the apical cell surface. In the bladder, the urothelium adapts to the cyclical changes of luminal contents and must maintain the permeability barrier under variations in pressure during filling and voiding. The permeability barrier (“blood-urine barrier”) between tissue fluids and urine depends on the high-resistance tight junctions between the superficial cells, and on their unique apical plasma membrane visible under the electron microscope.
The survey electron micrograph of a segment of the mouse urothelium in panel A shows three cell layers containing basal cells in the lower part of the picture, neighbored by intermediate cells in the middle part of the micrograph, and an umbrella cell in superficial position. The wrinkly apical surface of the umbrella cell visible in the transmission electron micrograph in panel A is shown in scanning micrographs in panels B and C. The arrows in the rectangle in panel B label the borders between three neighboring umbrella cells. The wrinkly character of the luminal surfaces of the umbrella cells, indicated by arrowheads in the circle, is achieved by the scalloped membrane formations shown at higher magnification in panel C. A particular area marked by a rectangle is further enlarged in the inset. Multiple ridges and microplicae are visible corresponding to the “hinge” regions of the scalloped formations, which are seen as small concave areas. The scalloped membrane formations are covered almost entirely with plaques consisting of two-dimensional crystals of hexagonally packed 16 nm particles composed of uroplakins (UP), a family of at least five proteins that include the tetraspan proteins UPIa and UPIb and the type I single-span proteins UPII, UPIIIa, and UPIIIb. The formation of correct heterodimers (UPIa/UPII and UPIb/UPIII) is required for uroplakins to exit from the endoplasmic reticulum on their way to the cell surface. In the trans Golgi network, heterodimers interact to form heterotetramers (UPIa/UPII-UPIb/UPIII) before they leave the Golgi apparatus to form 16 nm particles. Morphologically, plaque areas are characterized by an asymmetric unit membrane (AUM), shown in the inset in panel A. Because of the particular shapes and locations of the uroplakin particles, the outer membrane leaflet seems about twice as thick as the inner leaflet. The plaques constitute a main part of the barrier system of the urothelium. In the center of the scanning micrograph in panel C, the borders between three adjacent cells are visible as thin lines. Here, the cells are connected by complexes of tight and adhering junctions.