Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) channels. Taken together, this led us to hypothesize that Piezos may be able to signal their conformational state to other nearby proteins. Here, we use chemical control to acutely restrict Piezo1 conformational flexibility and show that Piezo1 conformational changes, but not ion permeation through them, are required for modulating the K2P channel K2P2.1 (TREK1). Super-resolution imaging and stochastic simulations further reveal that both channels do not co-localize, which implies that modulation is not mediated through direct binding interactions; however, at high Piezo1 densities, most TREK1 channels are within the predicted Piezo1 membrane footprint, suggesting that the footprint may underlie conformational signaling. We speculate that physiological roles originally attributed to Piezo1 ionotropic function could, alternatively, involve conformational signaling.

中文翻译：

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Piezo1 离子通道能够发出构象信号


Piezo1 是一种机械激活的离子通道，能够以短延迟和高灵敏度感应力。压电材料会发生较大的构象变化，引起膜上的深远变形，并调节双孔钾 (K2P) 通道的功能。综上所述，这使我们推测压电可能能够向附近的其他蛋白质发出其构象状态的信号。在这里，我们使用化学控制来严格限制 Piezo1 构象灵活性，并表明调节 K2P 通道 K2P2.1 (TREK1) 需要 Piezo1 构象变化，而不是离子渗透。超分辨率成像和随机模拟进一步表明，两个通道并不共定位，这意味着调制不是通过直接结合相互作用介导的；然而，在高 Piezo1 密度下，大多数 TREK1 通道位于预测的 Piezo1 膜足迹内，表明该足迹可能是构象信号传导的基础。我们推测最初归因于 Piezo1 离子传递功能的生理作用可能涉及构象信号传导。