TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration
- University of New South Wales, Australia
- Max Delbruck Center for Molecular Medicine, Germany
- Victor Chang Cardiac Research Institute, Australia
- Freie Universitat Berlin, Germany
- EMBL Australia, Australia
- Max Delbrück Center for Molecular Medicine, Germany
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
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
- Baron Chanda, University of Wisconsin-Madison, United States
Version history
- Received: November 4, 2019
- Accepted: March 28, 2020
- Accepted Manuscript published: March 31, 2020 (version 1)
- Accepted Manuscript updated: April 1, 2020 (version 2)
- Version of Record published: April 21, 2020 (version 3)
- 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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TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration
eLife 9:e53308.
https://doi.org/10.7554/eLife.53308
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