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.
Elife. 2020 Apr 1;9:e53308. doi: 10.7554/eLife.53308.
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.
机械转导是一种细胞信号通路，其中物理刺激通过机械激活的离子通道转化为电化学反应信号。我们在这里描述了黑色素瘤细胞中存在依赖于 TMEM87a（我们将其重新命名为 Elkin1）的机械激活电流。在缺乏 PIEZO1 的细胞（这些细胞没有基线机械敏感性）中表达这种蛋白足以重建机械激活电流。缺乏功能性 Elkin1 的黑色素瘤细胞表现出机械转导缺陷、运动能力下降以及从器官样球体解离增加。通过分析细胞黏附特性，我们证明 Elkin1 缺失与细胞-基质黏附增加和细胞间黏附强度降低有关。因此，我们得出结论，Elkin1 支持一种独立于 PIEZO1 的机械转导途径，并调节细胞黏附和调节黑色素瘤细胞迁移和细胞间相互作用。
