TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration
Amrutha Patkunarajah,
Jeffrey H Stear,
Mirko Moroni,
Lioba Schroeter,
Jedrzej Blaszkiewicz,
Jacqueline LE Tearle,
Charles D Cox,
Carina Fürst,
Oscar Sánchez-Carranza,
María del Ángel Ocaña Fernández,
Raluca Fleischer,
Murat Eravci,
Christoph Weise,
Boris Martinac,
Maté Biro,
Gary R Lewin,
Kate Poole
Affiliations
Amrutha Patkunarajah
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; Cellular and Systems Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia
Jeffrey H Stear
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
Mirko Moroni
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
Lioba Schroeter
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; Cellular and Systems Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia
Jedrzej Blaszkiewicz
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
Jacqueline LE Tearle
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia
Charles D Cox
Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent’s Clinical School, University of New South Wales, Darlinghurst, Australia
Carina Fürst
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
Oscar Sánchez-Carranza
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
María del Ángel Ocaña Fernández
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
Raluca Fleischer
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
Murat Eravci
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Berlin, Germany
Christoph Weise
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Berlin, Germany
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; Cellular and Systems Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia; Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia
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.
