TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration

eLife

Jacqueline LE Tearle¹  Maté Biro²  Lioba Schroeter³  Amrutha Patkunarajah³  Kate Poole⁴  Jeffrey H Stear⁵  Murat Eravci⁶  Christoph Weise⁶  Gary R Lewin⁷  Carina Fürst⁷  Raluca Fleischer⁷  Oscar Sánchez-Carranza⁷  Jedrzej Blaszkiewicz⁷  Maria del Angel Ocana Fernandez⁷  Mirko Moroni⁷  Charles D Cox⁸  Boris Martinac⁸ 

[1] EMBL Australia Node in Single Molecule Science, School of Medical Sciences, 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;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;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;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;Freie Universität Berlin, Institute of Chemistry and Biochemistry, Berlin, Germany;Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany;Victor Chang Cardiac Research Institute, Sydney, Australia;St Vincent’s Clinical School, University of New South Wales, Darlinghurst, Australia;

关键词: mechanically activated ion channels;    mechanotransduction;    cell migration;    cell adhesion;    melanoma;    Human;   

DOI  :  10.7554/eLife.53308

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY