Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels

Abstract

Mechanical stimuli drive many physiological processes, including touch and pain sensation, hearing, and blood pressure regulation. Mechanically-activated (MA) cation channel activities have been recorded in many cells, but the responsible molecules have not been identified. We characterized a rapidly-adapting MA current in a mouse neuroblastoma cell line. Expression profiling and RNAi knockdown of candidate genes identified Piezo1 (Fam38A) to be required for MA currents in these cells. Piezo1 and related Piezo2 (Fam38B) are vertebrate multipass transmembrane proteins with homologs in invertebrates, plants, and protozoa. Overexpression of mouse Piezo1 or Piezo2 induced two kinetically-distinct MA currents. Piezos are expressed in several tissues, and knockdown of Piezo2 in dorsal root ganglia neurons specifically reduced rapidly-adapting MA currents. We propose that Piezos are components of mechanically-activated cation channels.

Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells

“…Transfection of two previously validated short interfering RNAs (siRNAs) [25] into PCT cells, resulted in a Piezo1 knockdown of approximately 70-80% without affecting Pkd1, Pkd2 or other TRP channel subunits expression (supplementary Fig S1 online). SAC activity was strongly reduced in those transfected cells (Fig 2B).…”

“…Oligonucleotide sequences are available on request. siRNAs directed against Piezo1 have been previously validated (initially called siRNA1 and siRNA3) in [25] and transfected in PCT cells using the HiPerFect Transfection Reagent (Qiagen SA, Courtaboeuf, France). Electrophysiology.…”

Détecter la pression ?

“…Nos travaux ont permis de découvrir une famille de protéines qui sont impliquées directement dans l'étape initiale de la mécanotransduction [7], et qui constituent des cibles importantes dans l'exploration des fonctions affectées par les stimulations mécaniques. …”

Demystifying Mechanosensitive Piezo Ion Channels

“…They have been postulated to serve as a key set of mechanotransducers that convert mechanical stimuli into biological activities such as touch, hearing, proprioception, and blood-pressure regulation [1]. However, the molecular identities of mechanosensitive cation channels in mammals remained mysterious until the identification of the evolutionarilyconserved Piezo family of proteins, including Piezo1 and Piezo2, by Patapoutian and colleagues in 2010 [2]. This landmark discovery has heralded a new era for exploring the physiological significance and molecular mechanisms of mechanosensitive cation channels in mammals [3].…”

“…In particular, it remains a mystery as to how Piezo proteins function as mechanosensitive cation channels at the molecular level. Piezos are large transmembrane proteins with [2500 amino-acids and 30-40 putative transmembrane segments [2,4]. They do not possess notable sequence homology with any known class of ion channels.…”