Primary cilia regulate the osmotic stress response of renal epithelial cells through TRPM3.

Primary cilia regulate the osmotic stress response of renal epithelial cells through TRPM3. Am J Physiol Renal Physiol. 2017 Jan 25;:ajprenal.00465.2015 Authors: Siroky BJ, Kleene NK, Kleene SJ, Varnell CD, Comer RG, Liu J, Lu L, Pachciarz NW, Bissler JJ, Dixon BP Abstract Primary cilia sense environmental conditions including osmolality, but whether cilia participate in osmotic response in renal epithelial cells is not known. Transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells, and that ciliary TRPM3 and TRPV4 mediate that response. Ciliated (mIMCD-3 and 176-5) and non-ciliated (176-5∆) renal cells expressed Trpv4 and Trpm3 Ciliary expression of TRPM3 was observed in mIMCD-3 and 176-5 cells and in wildtype mouse kidney tissue. TRPV4 was identified in cilia and apical membrane of mIMCD-3 cells by electrophysiology, and in the cell body by immunofluorescence. Hyperosmolal stress at 500 mOsm/kg (via NaCl addition) induced the osmotic response genes Bgt1 and Akr1b3 in all ciliated cell lines. This induction was attenuated in non-ciliated cells. A TRPV4 agonist abrogated Bgt1 and Akr1b3 induction in ciliated and non-ciliated cells. A TRPM3 agonist attenuated Bgt1 and Akr1b3 induction...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research