Abstract
Urothelial plaques are specialized membrane domains in urothelial superficial (umbrella) cells, composed of highly ordered uroplakin particles. We investigated membrane compartments involved in the formation of urothelial plaques in mouse umbrella cells. The Golgi apparatus did not contain uroplakins organized into plaques. In the post-Golgi region, three distinct membrane compartments containing uroplakins were characterized: i) Small rounded vesicles, located close to the Golgi apparatus, were labelled weakly with anti-uroplakin antibodies and they possessed no plaques; we termed them “uroplakin-positive transporting vesicles” (UPTVs). ii) Spherical-to-flattened vesicles, termed “immature fusiform vesicles” (iFVs), were uroplakin-positive in their central regions and contained small urothelial plaques. iii) Flattened “mature fusiform vesicles” (mFVs) contained large plaques, which were densely labelled with anti-uroplakin antibodies. Endoytotic marker horseradish peroxidase was not found in these post-Golgi compartments. We propose a detailed model of de novo urothelial plaque formation in post-Golgi compartments: UPTVs carrying individual 16-nm particles detach from the Golgi apparatus and subsequently fuse into iFV. Concentration of 16-nm particles into plaques and removal of uroplakin-negative membranes takes place in iFVs. With additional fusions and buddings, iFVs mature into mFVs, each carrying two urothelial plaques toward the apical surface of the umbrella cell.
Highlights
Differentiation of the mammalian urothelium reaches its peak in the superficial cell layer, which consists of large umbrella cells [1,2,3]
We showed that plaques in the biosynthetic pathway form gradually in the individual post-Golgi compartments, termed: ‘‘uroplakinpositive transporting vesicles’’, ‘‘immature fusiform vesicles’’, and ‘‘mature fusiform vesicles’’
We propose a novel model of urothelial plaque formation, which includes the fusion of post-Golgi compartments, sorting of uroplakin-positive membranes and removal of uroplakin-negative membranes
Summary
Differentiation of the mammalian urothelium reaches its peak in the superficial cell layer, which consists of large umbrella cells [1,2,3]. Umbrella cells are unique for their luminal plasma membrane, as 70–90% of its area is covered by urothelial plaques [4,5,6]. The organization of uroplakins (UPs) in plaques [12,13] defines their rigidity [14,15] and is of major importance for the proper formation and maintenance of the urinary bladder’s permeability barrier [16,17,18,19]. Urothelial plaques are present in fusiform vesicles (FVs), each containing two plaques [1,11,20,21]. FVs function as transporting compartments for the delivery of urothelial plaques to the apical plasma membrane [22,23,24,25,26,27,28]. Mechanoreceptors activate exocytosis of FVs by purinergic signalling, modulated by cAMP, Ca2, extracellular ATP, adenosine, the epidermal growth factor receptors and the actin cytoskeleton [29]
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