Piezo1 ion channel pore properties are dictated by C-terminal region
Piezo1 and Piezo2 encode mechanically activated cation channels that function as mechanotransducers involved in vascular system development and touch sensing, respectively. Structural features of Piezos remain unknown. Mouse Piezo1 is bioinformatically predicted to have 30–40 transmembrane (TM) doma...
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| Format: | Online |
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Nature Pub. Group
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445471/ |
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pubmed-44454712015-06-18 Piezo1 ion channel pore properties are dictated by C-terminal region Coste, Bertrand Murthy, Swetha E. Mathur, Jayanti Schmidt, Manuela Mechioukhi, Yasmine Delmas, Patrick Patapoutian, Ardem Article Piezo1 and Piezo2 encode mechanically activated cation channels that function as mechanotransducers involved in vascular system development and touch sensing, respectively. Structural features of Piezos remain unknown. Mouse Piezo1 is bioinformatically predicted to have 30–40 transmembrane (TM) domains. Here, we find that nine of the putative inter-transmembrane regions are accessible from the extracellular side. We use chimeras between mPiezo1 and dPiezo to show that ion-permeation properties are conferred by C-terminal region. We further identify a glutamate residue within a conserved region adjacent to the last two putative TM domains of the protein, that when mutated, affects unitary conductance and ion selectivity, and modulates pore block. We propose that this amino acid is either in the pore or closely associates with the pore. Our results describe important structural motifs of this channel family and lay the groundwork for a mechanistic understanding of how Piezos are mechanically gated and conduct ions. Nature Pub. Group 2015-05-26 /pmc/articles/PMC4445471/ /pubmed/26008989 http://dx.doi.org/10.1038/ncomms8223 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Coste, Bertrand Murthy, Swetha E. Mathur, Jayanti Schmidt, Manuela Mechioukhi, Yasmine Delmas, Patrick Patapoutian, Ardem |
| spellingShingle |
Coste, Bertrand Murthy, Swetha E. Mathur, Jayanti Schmidt, Manuela Mechioukhi, Yasmine Delmas, Patrick Patapoutian, Ardem Piezo1 ion channel pore properties are dictated by C-terminal region |
| author_facet |
Coste, Bertrand Murthy, Swetha E. Mathur, Jayanti Schmidt, Manuela Mechioukhi, Yasmine Delmas, Patrick Patapoutian, Ardem |
| author_sort |
Coste, Bertrand |
| title |
Piezo1 ion channel pore properties are dictated by C-terminal region |
| title_short |
Piezo1 ion channel pore properties are dictated by C-terminal region |
| title_full |
Piezo1 ion channel pore properties are dictated by C-terminal region |
| title_fullStr |
Piezo1 ion channel pore properties are dictated by C-terminal region |
| title_full_unstemmed |
Piezo1 ion channel pore properties are dictated by C-terminal region |
| title_sort |
piezo1 ion channel pore properties are dictated by c-terminal region |
| description |
Piezo1 and Piezo2 encode mechanically activated cation channels that function as mechanotransducers involved in vascular system development and touch sensing, respectively. Structural features of Piezos remain unknown. Mouse Piezo1 is bioinformatically predicted to have 30–40 transmembrane (TM) domains. Here, we find that nine of the putative inter-transmembrane regions are accessible from the extracellular side. We use chimeras between mPiezo1 and dPiezo to show that ion-permeation properties are conferred by C-terminal region. We further identify a glutamate residue within a conserved region adjacent to the last two putative TM domains of the protein, that when mutated, affects unitary conductance and ion selectivity, and modulates pore block. We propose that this amino acid is either in the pore or closely associates with the pore. Our results describe important structural motifs of this channel family and lay the groundwork for a mechanistic understanding of how Piezos are mechanically gated and conduct ions. |
| publisher |
Nature Pub. Group |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445471/ |
| _version_ |
1613228197352046592 |