Piezo1 ion channel pore properties are dictated by C-terminal region
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Piezo1 is non-selective, allowing the permeation of univalent cations, such as K+ and Na+, along with divalent cations, such as Ca2+ and Mg2+, displaying a bias toward Ca2+.
“Piezo1 is non-selective, allowing the permeation of univalent cations, such as K+ and Na+, along with divalent cations, such as Ca2+ and Mg2+, displaying a bias toward Ca2+.22,29,30”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [30]
The Results sections describe mPiezo1 as a non-selective cation channel and report calcium permeability, with a PCa/PCs ratio of 1.21 indicating a slight preference for calcium over cesium. The paper does not establish permeability to Mg2+ or K+, or a calcium preference over each of the ions listed in the claim; their presence in the Methods solutions alone does not establish permeation. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 36 · Cited by 239
Research works printed but not linked: 36
- Kim S. E., Coste B., Chadha A., Cook B. & Patapoutian A. The role of Drosophila Piezo in mechanical nociception. Nature 483, 209– 212 (2012). 22343891 PMC3297676
- Faucherre A., Nargeot J., Mangoni M. E. & Jopling C. piezo2b regulates vertebrate light touch response. J. Neurosci. 33, 17089– 17094 (2013). 24155313 PMC6618434
- Ikeda R. et al. Merkel cells transduce and encode tactile stimuli to drive abeta-afferent impulses. Cell 157, 664– 675 (2014). 24746027 PMC4003503
- Maksimovic S. et al. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509, 617– 621 (2014). 24717432 PMC4097312
- Woo S. H. et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622– 626 (2014). 24717433 PMC4039622
- Ranade S. S. et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516, 121– 125 (2014). 25471886 PMC4380172
- Faucherre A., Kissa K., Nargeot J., Mangoni M. E. & Jopling C. Piezo1 plays a role in erythrocyte volume homeostasis. Haematologica 99, 70– 75 (2014). PMC4007942 23872304
- Li J. et al. Piezo1 integration of vascular architecture with physiological force. Nature 515, 279– 282 (2014). 25119035 PMC4230887
- Ranade S. S. et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc. Natl Acad. Sci. USA 111, 10347– 10352 (2014). 24958852 PMC4104881
- Albuisson J. et al. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat. Commun. 4, 1884 (2013). 23695678 PMC3674779
- Bae C., Gnanasambandam R., Nicolai C., Sachs F. & Gottlieb P. A. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. Proc. Natl Acad. Sci. USA 110, E1162– E1168 (2013). 23487776 PMC3606986
- Coste B. et al. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of distal Arthrogryposis. Proc. Natl Acad. Sci. USA 110, 4667– 4672 (2013). 23487782 PMC3607045
- Coste B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55– 60 (2010). 20813920 PMC3062430
- Coste B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176– 181 (2012). 22343900 PMC3297710
- Kamajaya A., Kaiser J. T., Lee J., Reid M. & Rees D. C. The structure of a conserved piezo channel domain reveals a topologically distinct beta sandwich fold. Structure 22, 1520– 1527 (2014). 25242456 PMC4192063
- Volkers L., Mechioukhi Y. & Coste B. Piezo channels: from structure to function. Pflugers Arch. 467, 95– 99 (2014). 25037583
- Schmidt M., Dubin A. E., Petrus M. J., Earley T. J. & Patapoutian A. Nociceptive signals induce trafficking of TRPA1 to the plasma membrane. Neuron 64, 498– 509 (2009). 19945392 PMC2854037
- Voets T. & Nilius B. The pore of TRP channels: trivial or neglected? Cell Calcium 33, 299– 302 (2003). 12765676
- Brelidze T. I., Niu X. & Magleby K. L. A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification. Proc. Natl Acad. Sci. USA 100, 9017– 9022 (2003). 12843404 PMC166430
- Hansen S. B., Wang H. L., Taylor P. & Sine S. M. An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance. J. Biol. Chem. 283, 36066– 36070 (2008). 18940802 PMC2662287
- Kellenberger S., Auberson M., Gautschi I., Schneeberger E. & Schild L. Permeability properties of ENaC selectivity filter mutants. J. Gen. Physiol. 118, 679– 692 (2001). 11723161 PMC2229513
- Kang L., Gao J., Schafer W. R., Xie Z. & Xu X. Z. C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel. Neuron 67, 381– 391 (2010). 20696377 PMC2928144
- Yan Z. et al. Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Nature 493, 221– 225 (2013). 23222543 PMC3917554
- Owsianik G., Talavera K., Voets T. & Nilius B. Permeation and selectivity of TRP channels. Annu. Rev. Physiol. 68, 685– 717 (2006). 16460288
- Liao M., Cao E., Julius D. & Cheng Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504, 107– 112 (2013). 24305160 PMC4078027
- Garcia-Martinez C., Morenilla-Palao C., Planells-Cases R., Merino J. M. & Ferrer-Montiel A. Identification of an aspartic residue in the P-loop of the vanilloid receptor that modulates pore properties. J. Biol. Chem. 275, 32552– 32558 (2000). 10931826
- Voets T. et al. Molecular determinants of permeation through the cation channel TRPV4. J. Biol. Chem. 277, 33704– 33710 (2002). 12093812
- MacKinnon R. & Miller C. Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor. Science 245, 1382– 1385 (1989). 2476850
- Andolfo I. et al. Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood 121, 3925– 3935 (2013). 23479567
- Bagriantsev S. N., Gracheva E. O. & Gallagher P. G. Piezo proteins: regulators of mechanosensation and other cellular processes. J. Biol. Chem. 289, 31673– 31681 (2014). 25305018 PMC4231648
- Delmas P. & Coste B. Mechano-gated ion channels in sensory systems. Cell 155, 278– 284 (2013). 24120130
- Nilius B. & Honore E. Sensing pressure with ion channels. Trends Neurosci. 35, 477– 486 (2012). 22622029
- Prole D. L. & Taylor C. W. Identification and analysis of putative homologues of mechanosensitive channels in pathogenic protozoa. PLoS ONE 8, e66068 (2013). 23785469 PMC3681921
- Xiao R. & Xu X. Z. Mechanosensitive channels: in touch with Piezo. Curr. Biol. 20, R936– R938 (2010). 21056836 PMC3018681
- Zarychanski R. et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 120, 1908– 1915 (2012). 22529292 PMC3448561
- Dutzler R., Campbell E. B., Cadene M., Chait B. T. & MacKinnon R. X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. Nature 415, 287– 294 (2002). 11796999
- Authors
- Coste, B., Murthy, S. E., Mathur, J., Schmidt, M., Mechioukhi, Y., Delmas, P., & Patapoutian, A.
- Affiliations
- Scripps Research Institute (US)
- Genomics Institute of the Novartis Research Foundation (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Coste, Bertrand
- Venue
- Nature Communications
- Published
- 2015-05-26
- Volume
- 6
- Issue
- 1
- Pages
- 7223-7223
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4445471
- OpenAlex
- W2260991120
- Cited by
- 239
- References
- 36
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 27 · 2023: 12 · 2022: 22 · 2021: 27 · 2020: 16 · 2019: 31 · 2018: 19 · 2017: 22 · 2016: 21 · 2015: 8 · 2012: 1
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- HAL AMU (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Agence Nationale de la Recherche (ANR-12-PDOC-0005, ANR-12)
- National Institutes of Health (NS083174)
- National Institute of Neurological Disorders and Stroke (NS083174, R01NS083174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Keywords
- Piezo1, Piezo2, mechanosensitive ion channels, C-terminal region, ion selectivity, single-channel conductance, pore blocking, glutamate residues, transmembrane domain, chimeric channels, mechanotransduction, tactile sensing, vascular development
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Ion Channels, Molecular Sequence Data, Drosophila Proteins, Mice, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
