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lüll The mechanoreceptor TRPV4 is localized in adherence junctions of the human bladder urothelium: a morphological study Janssen DA; Hoenderop JG; Jansen KC; Kemp AW; Heesakkers JP; Schalken JAJ Urol 2011[Sep]; 186 (3): 1121-7PURPOSE: TRPV4 (transient receptor potential vanilloid 4 channel) is a nonselective cation channel involved in different sensory functions that was recently implicated in bladder mechanosensation. We investigated the cellular site of TRPV4 in bladder urothelium and explored a molecular connection between TRPV4 and urothelial adherence junctions. MATERIALS AND METHODS: We obtained healthy tissues sections from cystectomy in humans due to cancer in 3 and noncancerous conditions in 2. Besides human biopsies tissues from 7 normal and 7 TRPV4-/-mice, and the urothelial cell line RT4 were also used. Experiments were done with polyclonal antibody against TRPV4 (against the N-terminus of rat TRPV4). A molecular connection between TRPV4 and different adherence junction components was investigated using immunofluorescence, Western blot and immunoprecipitation. RESULTS: Results revealed TRPV4 on urothelial cell membranes near adherence junctions. Results were comparable in the urothelial cell line, human bladders and mouse bladders. Subsequent immunoprecipitation experiments established a molecular connection of TRPV4 to alpha-catenin, an integral part of the adherence junction that catenates E-cadherin to the actin-microfilament network. CONCLUSIONS: Results provide evidence for the location of TRPV4 in human bladder urothelium. TRPV4 is molecularly connected to adherence junctions on the urothelial cell membrane. TRPV4 coupling to a rigid intracellular and intercellular structural network would agree with the hypothesis that TRPV4 can be activated by bladder stretch.|Adherens Junctions/*chemistry[MESH]|Animals[MESH]|Cells, Cultured[MESH]|Humans[MESH]|Mice[MESH]|Rats[MESH]|TRPV Cation Channels/*analysis[MESH]|Urinary Bladder/*chemistry[MESH]|Urothelium/*chemistry[MESH] |