Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells. (25th October 2013)

• Record Type: Journal Article
• Authors: Peyronnet, Rémi; Martins, Joana R; Duprat, Fabrice; Demolombe, Sophie; Arhatte, Malika; Jodar, Martine; Tauc, Michel; Duranton, Christophe; Paulais, Marc; Teulon, Jacques; Honoré, Eric; Patel, Amanda
• Is Part Of: EMBO reports. Volume 14:Number 12(2013)
• Page Start: 1143
• Page End: 1148
• Publication Date: 2013-10-25
• Subjects: Fam38A -- kidney -- Piezo1 -- PKD -- mechanotransduction -- TRP channels; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.1038/embor.2013.170
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract : Mechanical forces associated with fluid flow and/or circumferential stretch are sensed by renal epithelial cells and contribute to both adaptive or disease states. Non‐selective stretch‐activated ion channels (SACs), characterized by a lack of inactivation and a remarkably slow deactivation, are active at the basolateral side of renal proximal convoluted tubules. Knockdown of Piezo1 strongly reduces SAC activity in proximal convoluted tubule epithelial cells. Similarly, overexpression of Polycystin‐2 (PC2) or, to a greater extent its pathogenic mutant PC2‐740X, impairs native SACs. Moreover, PC2 inhibits exogenous Piezo1 SAC activity. PC2 coimmunoprecipitates with Piezo1 and deletion of its N‐terminal domain prevents both this interaction and inhibition of SAC activity. These findings indicate that renal SACs depend on Piezo1, but are critically conditioned by PC2. Abstract : This study provides evidence that the activity of renal non‐selective stretch‐activated ion channels (SACs) depends on Piezo1 but is negatively regulated by Polycystin‐2 (PC2). PC2 co‐immunoprecipitates with Piezo1 and deletion of its N‐terminal domain prevents both this interaction and inhibition of SAC activity.