1. Cancer Biology
  2. Cell Biology
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TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration

  1. Amrutha Patkunarajah
  2. Jeffrey H Stear
  3. Mirko Moroni
  4. Lioba Schroeter
  5. Jedrzej Blaszkiewicz
  6. Jacqueline LE Tearle
  7. Charles D Cox
  8. Carina Fuerst
  9. Oscar Sanchez-Carranza
  10. María del Ángel Ocaña Fernández
  11. Raluca Fleischer
  12. Murat Eravci
  13. Christoph Weise
  14. Boris Martinac
  15. Maté Biro
  16. Gary R Lewin
  17. Kate Poole  Is a corresponding author
  1. University of New South Wales, Australia
  2. Max Delbruck Center for Molecular Medicine, Germany
  3. Victor Chang Cardiac Research Institute, Australia
  4. Freie Universitat Berlin, Germany
  5. EMBL Australia, Australia
  6. Max Delbrück Center for Molecular Medicine, Germany
Research Article
  • Cited 14
  • Views 2,855
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Cite this article as: eLife 2020;9:e53308 doi: 10.7554/eLife.53308

Abstract

Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels. We describe here the presence of mechanically activated currents in melanoma cells that are dependent on TMEM87a, which we have renamed Elkin1. Heterologous expression of this protein in PIEZO1-deficient cells, that exhibit no baseline mechanosensitivity, is sufficient to reconstitute mechanically activated currents. Melanoma cells lacking functional Elkin1 exhibit defective mechanoelectrical transduction, decreased motility and increased dissociation from organotypic spheroids. By analysing cell adhesion properties, we demonstrate that Elkin1 deletion is associated with increased cell-substrate adhesion and decreased homotypic cell-cell adhesion strength. We therefore conclude that Elkin1 supports a PIEZO1-independent mechanoelectrical transduction pathway and modulates cellular adhesions and regulates melanoma cell migration and cell-cell interactions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data file has been provided for figures 1, 3, 4, 6, 7, 8. Proteomics data provided as supplementary table 1

Article and author information

Author details

  1. Amrutha Patkunarajah

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Jeffrey H Stear

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Mirko Moroni

    Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Lioba Schroeter

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Jedrzej Blaszkiewicz

    Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Jacqueline LE Tearle

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Charles D Cox

    Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Carina Fuerst

    Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Oscar Sanchez-Carranza

    Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. María del Ángel Ocaña Fernández

    Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Raluca Fleischer

    Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Murat Eravci

    Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Christoph Weise

    Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Boris Martinac

    Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8422-7082
  15. Maté Biro

    Single Molecule Science node, School of Medical Sciences, EMBL Australia, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5852-3726
  16. Gary R Lewin

    Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2890-6352
  17. Kate Poole

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    For correspondence
    k.poole@unsw.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0879-6093

Funding

National Health and Medical Research Council (APP1138595)

  • Boris Martinac
  • Maté Biro
  • Kate Poole

Deutsche Forschungsgemeinschaft (SFB958,project A09)

  • Gary R Lewin
  • Kate Poole

National Health and Medical Research Council (APP1135974)

  • Boris Martinac

Deutsche Forschungsgemeinschaft (SFB958,project Z03)

  • Murat Eravci
  • Christoph Weise

Humboldt Foundation (Postdoctoral Fellowship)

  • Mirko Moroni

Max Delbruck Center (Cecile Vogt Fellowship)

  • Kate Poole

Department of Education, Australian Government (RTP scholarship)

  • Amrutha Patkunarajah

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: November 4, 2019
  2. Accepted: March 28, 2020
  3. Accepted Manuscript published: March 31, 2020 (version 1)
  4. Accepted Manuscript updated: April 1, 2020 (version 2)
  5. Version of Record published: April 21, 2020 (version 3)
  6. Version of Record updated: April 22, 2020 (version 4)

Copyright

© 2020, Patkunarajah 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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