Piezo1 ion channels are capable of conformational signaling

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 it, are
required for modulating the K2P channel 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
the footprint may underlie conformational signaling. We speculate that
physiological roles originally attributed to Piezo1 ionotropic function
could, alternatively, involve conformational signaling.

Piezo1是一种机械激活离子通道（mechanically activated ion channel），能够以极短潜伏期与高灵敏度感知机械力。Piezo家族通道会发生大规模构象变化，对细胞膜造成大范围形变，并调控双孔钾离子（two-pore potassium, K2P）通道的功能。综上，我们提出如下假说：Piezo家族通道可向邻近其他蛋白传递自身构象状态的信号。本研究通过化学调控手段瞬时限制Piezo1的构象灵活性，实验证实：调控K2P通道TREK1需要Piezo1发生构象变化，而非其介导的离子渗透过程。超分辨率成像（super-resolution imaging）与随机模拟（stochastic simulations）进一步揭示，两类通道并未发生共定位，这意味着该调控并非通过直接结合相互作用介导；然而，当Piezo1表达密度较高时，绝大多数TREK1通道均处于预测的Piezo1膜足迹（membrane footprint）范围内，这提示该足迹可能是构象信号传递的结构基础。我们推测，原本被归因于Piezo1离子通道型功能的生理作用，也可通过构象信号传递途径实现。