I am a
Home I AM A Search Login

Papers of the Week

Papers: 7 Mar 2020 - 13 Mar 2020

2020 Mar 05


A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.


Geng J, Liu W, Zhou H, Zhang T, Wang L, Zhang M, Li Y, Shen B, Li X, Xiao B
Neuron. 2020 Mar 05.
PMID: 32142647.


The mechanosensitive Piezo1 and Piezo2 channels convert mechanical force into cation permeation. However, their precise mechanogating and regulatory mechanisms remain elusive. Here, we report that Piezo1 utilizes three lateral ion-conducting portals equipped with physical gates for cooperative gating and splicing regulation. Mutating residues lining the portal converts Piezo1 into an anion-selective channel, demonstrating the portal-based cation-permeating pathway. Intriguingly, the portal is physically blocked with a plug domain, which undergoes alternative splicing in both Piezo1 and Piezo2. The Piezo1 isoform has local openings of the portals, enlarged single-channel conductance and sensitized mechanosensitivity. Remarkably, the three plugs are strategically latched onto the central axis for coordinated gating of the three portals. Disrupting the latching induces three quantal sub-conductance states in Piezo1, but not in the isoform. Together, we propose that Piezo utilizes an elegant plug-and-latch mechanism to physically and coordinately gate the lateral portals through the spliceable plug gates.