| First Author | Geng J | Year | 2020 |
| Journal | Neuron | Volume | 106 |
| Issue | 3 | Pages | 438-451.e6 |
| PubMed ID | 32142647 | Mgi Jnum | J:292721 |
| Mgi Id | MGI:6449305 | Doi | 10.1016/j.neuron.2020.02.010 |
| Citation | Geng J, et al. (2020) A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel. Neuron 106(3):438-451.e6 |
| abstractText | 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. |
