title: Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.
abstract: Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively.
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Qiancheng
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Geng
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Chi
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhi
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
authors.forename: Mingmin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China. Electronic address: xbailong@biomed.tsinghua.edu.cn.
authors.forename: Bailong
authors.initials: B
authors.lastname: Xiao
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004558:Electric Stimulation; D057809:HEK293 Cells; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007477:Ions / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008698:Mesylates / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D002712:Chlorides; D007202:Indicators and Reagents; D007473:Ion Channels; D007477:Ions; D008698:Mesylates; C552920:Piezo1 protein, mouse; D021122:Protein Subunits; C109153:(2-sulfonatoethyl)methanethiosulfonate; D002586:Cesium; C028019:cesium chloride; D002122:Calcium Chloride