1. Evolutionary Biology
  2. Structural Biology and Molecular Biophysics
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OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels

  1. Swetha E Murthy
  2. Adrienne E Dubin
  3. Tess Whitwam
  4. Sebastian Jojoa Cruz
  5. Stuart M Cahalan
  6. Seyed Ali Mosavi
  7. Andrew B Ward
  8. Ardem Patapoutian  Is a corresponding author
  1. The Scripps Research Institute, United States
Research Article
  • Cited 36
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Cite this article as: eLife 2018;7:e41844 doi: 10.7554/eLife.41844

Abstract

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

Article and author information

Author details

  1. Swetha E Murthy

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9580-3380

  2. Adrienne E Dubin

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Tess Whitwam

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Sebastian Jojoa Cruz

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4392-3898

  5. Stuart M Cahalan

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Seyed Ali Mosavi

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Andrew B Ward

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7153-3769

  8. Ardem Patapoutian

    Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
    For correspondence
    ardem@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0726-7034

Funding

National Institute of Neurological Disorders and Stroke (R35NS105067)

  • Ardem Patapoutian

Howard Hughes Medical Institute

  • Ardem Patapoutian

National Institutes of Health (R21DE025329)

  • Adrienne E Dubin

Ray Thomas Edwards Foundation

  • Andrew B Ward

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: September 8, 2018
  2. Accepted: October 11, 2018
  3. Accepted Manuscript published: November 1, 2018 (version 1)
  4. Version of Record published: November 14, 2018 (version 2)
  5. Version of Record updated: November 15, 2018 (version 3)

Copyright

© 2018, Murthy et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    Cryo-EM structure of the mechanically activated ion channel OSCA1.2

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    Mechanically activated ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure. OSCA/TMEM63s are a newly-identified family of eukaryotic mechanically activated ion channels opened by membrane tension. The structural underpinnings of OSCA/TMEM63 function are not explored. Here, we elucidate high resolution cryo-electron microscopy structures of OSCA1.2, revealing a dimeric architecture containing eleven transmembrane helices per subunit and surprising topological similarities to TMEM16 proteins. We locate the ion permeation pathway within each subunit by demonstrating that a conserved acidic residue is a determinant of channel conductance. Molecular dynamics simulations reveal membrane interactions, suggesting the role of lipids in OSCA1.2 gating. These results lay a foundation to decipher how the structural organization of OSCA/TMEM63 is suited for their roles as MA ion channels.

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