Patkunarajah, Amrutha and Stear, Jeffrey H and Moroni, Mirko and Schroeter, Lioba and Blaszkiewicz, Jedrzej and Tearle, Jacqueline LE and Cox, Charles D and Fuerst, Carina and Sanchez-Carranza, Oscar and Ocaña Fernández, María del Ángel and Fleischer, Raluca and Eravci, Murat and Weise, Christoph and Martinac, Boris and Biro, Maté and Lewin, Gary R and Poole, Kate (2020) TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration. eLife, 9. ISSN 2050-084X
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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.
Item Type: | Article |
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Subjects: | R Medicine > R Medicine (General) |
Depositing User: | Repository Administrator |
Date Deposited: | 06 Apr 2020 22:52 |
Last Modified: | 19 Oct 2021 00:28 |
URI: | http://eprints.victorchang.edu.au/id/eprint/954 |
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