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.

中文翻译：

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TMEM87a / Elkin1，一种新型的机电转导途径，调节黑色素瘤的粘附和迁移

机电转导是一种细胞信号传导途径，其中物理刺激通过机械激活的离子通道转化为电化学信号。我们在这里描述依赖于TMEM87a的黑色素瘤细胞中机械激活电流的存在，我们将其重命名为Elkin1。该蛋白在不具有基线机械敏感性的PIEZO1缺陷细胞中异源表达，足以重构机械激活的电流。缺乏功能性Elkin1的黑素瘤细胞表现出有缺陷的机电转换，运动性降低以及与器官型球体的解离增加。通过分析细胞粘附特性，我们证明Elkin1缺失与增加的细胞-基质粘附和降低的同型细胞-细胞粘附强度有关。