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

Neuron
Jie GengBailong Xiao

Abstract

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.

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Citations

Dec 29, 2020·The Journal of Biological Chemistry·Elena D NosyrevaRuhma Syeda
Jan 21, 2021·Communications Biology·Wenjuan JiangYun Lyna Luo
Feb 22, 2021·Trends in Biochemical Sciences·Yan JiangBailong Xiao
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Jul 3, 2021·International Journal of Molecular Sciences·Xia XuLifang Hu
Jul 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jie LiWei Xiong
Jul 9, 2021·Annual Review of Neuroscience·Ruhma Syeda
Jul 5, 2021·Current Opinion in Cell Biology·Vinay Swaminathan, Martijn Gloerich

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