title: Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells.
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.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Peyronnet
authors.forename: Joana R
authors.initials: JR
authors.lastname: Martins
authors.forename: Fabrice
authors.initials: F
authors.lastname: Duprat
authors.forename: Sophie
authors.initials: S
authors.lastname: Demolombe
authors.forename: Malika
authors.initials: M
authors.lastname: Arhatte
authors.forename: Martine
authors.initials: M
authors.lastname: Jodar
authors.forename: Michel
authors.initials: M
authors.lastname: Tauc
authors.forename: Christophe
authors.initials: C
authors.lastname: Duranton
authors.forename: Marc
authors.initials: M
authors.lastname: Paulais
authors.forename: Jacques
authors.initials: J
authors.lastname: Teulon
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
authors.forename: Amanda
authors.initials: A
authors.lastname: Patel
mesh_terms: D000200:Action Potentials; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology; D040542:Mechanotransduction, Cellular; D009154:Mutation; D011485:Protein Binding; D050052:TRPC Cation Channels / Q000378:metabolism; D050396:TRPP Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D050052:TRPC Cation Channels; D050396:TRPP Cation Channels; C515204:PIEZO1 protein, human