title: Piezo proteins are pore-forming subunits of mechanically activated channels.
abstract: Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ∼1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.
authors.affiliation: Department of Cell Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coste
authors.forename: Bailong
authors.initials: B
authors.lastname: Xiao
authors.forename: Jose S
authors.initials: JS
authors.lastname: Santos
authors.forename: Ruhma
authors.initials: R
authors.lastname: Syeda
authors.forename: Jörg
authors.initials: J
authors.lastname: Grandl
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Spencer
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidt
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mathur
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Dubin
authors.forename: Mauricio
authors.initials: M
authors.lastname: Montal
authors.forename: Ardem
authors.initials: A
authors.lastname: Patapoutian
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D004553:Electric Conductivity; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D016062:Porosity; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; C571430:Piezo protein, Drosophila; C552920:Piezo1 protein, mouse; D021122:Protein Subunits