Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells |
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Authors: | Rémi Peyronnet Joana R Martins Fabrice Duprat Sophie Demolombe Malika Arhatte Martine Jodar Michel Tauc Christophe Duranton Marc Paulais Jacques Teulon Eric Honoré Amanda Patel |
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Affiliation: | 1. Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, , Valbonne, France;2. CNRS‐FRE 472, Laboratoire de Physiomédecine Moléculaire, Université de Nice Sophia Antipolis, , Nice, France;3. UPMC Université Paris 06, UMR 872 CNRS, Laboratoire de Génomique, Physiologie et Physiopathologie Rénales, , Paris, France |
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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. |
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Keywords: | Fam38A kidney Piezo1 PKD mechanotransduction TRP channels |
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