Expression and localization of the mechanosensitive/osmosensitive ion channel TMEM63B in the mouse urinary tract

Author:

Dalghi Marianela G.1,DuRie Ella1,Ruiz Wily G.1,Clayton Dennis R.1,Montalbetti Nicolas1,Mutchler Stephanie B.1,Satlin Lisa M.2,Kleyman Thomas R.134ORCID,Carattino Marcelo D.13,Shi Yun Stone5,Apodaca Gerard13ORCID

Affiliation:

1. Department of Medicine and George M. O'Brien Pittsburgh Center for Kidney Research University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

2. Department of Pediatrics Icahn School of Medicine at Mount Sinai New York New York USA

3. Department of Cell Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

4. Department of Chemical Biology & Pharmacology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

5. Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School Nanjing University Nanjing China

Abstract

AbstractThe epithelial cells that line the kidneys and lower urinary tract are exposed to mechanical forces including shear stress and wall tension; however, the mechanosensors that detect and respond to these stimuli remain obscure. Candidates include the OSCA/TMEM63 family of ion channels, which can function as mechanosensors and osmosensors. Using Tmem63bHA‐fl/HA‐fl reporter mice, we assessed the localization of HA‐tagged‐TMEM63B within the urinary tract by immunofluorescence coupled with confocal microscopy. In the kidneys, HA‐TMEM63B was expressed by proximal tubule epithelial cells, by the intercalated cells of the collecting duct, and by the epithelial cells lining the thick ascending limb of the medulla. In the urinary tract, HA‐TMEM63B was expressed by the urothelium lining the renal pelvis, ureters, bladder, and urethra. HA‐TMEM63B was also expressed in closely allied organs including the epithelial cells lining the seminal vesicles, vas deferens, and lateral prostate glands of male mice and the vaginal epithelium of female mice. Our studies reveal that TMEM63B is expressed by subsets of kidney and lower urinary tract epithelial cells, which we hypothesize are sites of TMEM63B mechanosensation or osmosensation, or both.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Office of Extramural Research

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

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