Our observation of contacts between mFVs and the apical plasma membrane supports this hypothesis. Therefore, reorientations of mFVs might facilitate the insertion of mFVs into the apical plasma membrane. However, the methods used in this study do not allow the conclusions whether all FVs in the subapical cytoplasm are destined to be inserted into the apical plasma membrane. It is possible that some FVs are derived from the apical surface. Our results of Rab27b immunolabelling support the idea of two classes of FVs, i.e. exocytotic and endocytotic. However, the bladder state has no influence on the size and shape of the plaques. Reorganization of mFVs from stacks in the central cytoplasm to individual entities in the subapical cytoplasm might reflect distinct roles of mFVs; stacked FVs enable maturation and storage of plaques, while individual mFVs facilitate the transport and fusion of plaques with the apical plasma membrane. Similar reorganizations of cellular compartments during protein transport was observed also in some other urothelium non-related cell systems reorganization. Comparison with umbrella cells shows that intermediate cells contain vesicles that are smaller and less flattened as Epimedoside-A. They are weakly labelled with antibodies against uroplakins; they contain smaller plaques and therefore they represent iFVs. Interestingly, we could not detect fusions of iFVs with the plasma membrane of intermediate cells. A possible explanation for this is, that iFVs of intermediate cells lack a machinery for docking and/ or fusion like specific Rab and SNARE complexes. It can be stated that the maturation of FVs coincide with the terminal differentiation of urothelial cells. Smaller, more convex iFVs are therefore characteristic of partially differentiated intermediate cells, which contain less uroplakins and also lack cell surfaceassociated plaques. Large, flattened mFVs are typical compartments only of highly differentiated umbrella cells. In conclusion, we have shown here 3D ultrastructure and higher organization of FVs in the urothelial cells. mFVs, present exclusively in terminally differentiated umbrella cells, are flattened discs that are organised into Baohuoside-I stacks in the central cytoplasm. From there, individual mFVs can be transported to the subapical cytoplasm, where their orientation greatly depends on the distension-contraction cycle of the urinary bladders. Due to their shape and higher organization, mFVs act as ideal compartments, which can store and transport large amount of membranes while occupying minimal volume of umbrella cells. The pathological hallmark of PD is Lewy bodies, which are intracellular inclusion bodies consisting of aggregated alphasynuclein. Abnormal accumulation of aggregated protein is closely associated with the pathogenesis of many neurodegenerative diseases. The precise mechanism of aggregation remains unknown, but increased expression of aggregation-prone proteins can lead to their aggregation. For example, in Down syndrome, duplication of the 21st chromosome, which contains the amyloid beta precursor protein gene, leads to accumulation of amyloid beta and Alzheimer’s disease pathology. In rare cases of PD, duplication or triplication of SNCA gene leads to alphasynuclein accumulation, with triplication producing a more severe phenotype than duplication, suggesting that SNCA expression level determines the severity of the pathology. Animal models of neurodegenerative disorders are generated by over-expression of causal genes, further supporting the conclusion that increased gene expression is related to pathogenesis. Additional evidence indicates that SNCA promoter polymorphisms increases alphasynuclein expression and increases susceptibility to sporadic PD.