Abstract
The primary function of the urothelium is to provide the tightest and most impermeable barrier in the body, i.e. the blood-urine barrier. Urothelial plaques are formed and inserted into the apical plasma membrane during advanced stages of urothelial cell differentiation. Currently, it is supposed that differentiation with the final formation of urothelial plaques is hindered in cultured urothelial cells. With the aid of the high-resolution imaging technique of freeze-fracture replica immunolabelling, we here provide evidence that urothelial cells in vitro form uroplakin-positive urothelial plaques, localized in fusiform-shaped vesicles and apical plasma membranes. With the establishment of such an in vitro model of urothelial cells with fully developed urothelial plaques and functional properties equivalent to normal bladder urothelium, new perspectives have emerged which challenge prevailing concepts of apical plasma membrane biogenesis and blood-urine barrier development. This may hopefully provide a timely impulse for many ongoing studies and open up new questions for future research.
Highlights
Urothelial plaques are ultrastructurally distinctive, highly ordered structures made of crystalline arrays of 16-nm hexagon shaped protein particles consisting of four integral membrane proteins called uroplakins i.e. UPIa, UPIb, UPII and UPIIIa [1,2]
The latter are the most significant molecules in the apical plasma membrane (PM) of the differentiated urothelial cells (UCs) that line the urinary tract from the renal pelvis to the proximal urethra [3,4]
Uroplakins were previously found in cultured UCs [7,8,9,10,11], the prevailing view is that differentiation with the final formation of urothelial plaques is hindered in cultured UCs
Summary
Urothelial plaques are ultrastructurally distinctive, highly ordered structures made of crystalline arrays of 16-nm hexagon shaped protein particles consisting of four integral membrane proteins called uroplakins i.e. UPIa, UPIb, UPII and UPIIIa [1,2]. The latter are the most significant molecules in the apical plasma membrane (PM) of the differentiated urothelial cells (UCs) that line the urinary tract from the renal pelvis to the proximal urethra [3,4]. The widely held assumption that uroplakins do not form urothelial plaques in cultured UCs is based on immunofluorescence light microscopy and standard thin section electron microscopy (EM)
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