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A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.
Neuron ( IF 14.7 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.neuron.2020.02.010 Jie Geng 1 , Wenhao Liu 2 , Heng Zhou 3 , Tingxin Zhang 1 , Li Wang 1 , Mingmin Zhang 1 , Yiran Li 1 , Bo Shen 3 , Xueming Li 3 , Bailong Xiao 1
Neuron ( IF 14.7 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.neuron.2020.02.010 Jie Geng 1 , Wenhao Liu 2 , Heng Zhou 3 , Tingxin Zhang 1 , Li Wang 1 , Mingmin Zhang 1 , Yiran Li 1 , Bo Shen 3 , Xueming Li 3 , Bailong Xiao 1
Affiliation
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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.
中文翻译：
门控机械灵敏压电通道的即插即用机制。
机械敏感的Piezo1和Piezo2通道将机械力转换为阳离子渗透。但是，它们的精确机械化和调节机制仍然难以捉摸。在这里，我们报告Piezo1利用配备有物理门的三个侧向离子导电门户进行协作门控和剪接调节。门户内衬的突变残基将Piezo1转换成阴离子选择性通道，说明了基于门户的阳离子渗透途径。有趣的是，门户在物理上被插件域阻塞，该插件域在Piezo1和Piezo2中都经历了可变的剪接。Piezo1同工型具有门户的局部开口，增大的单通道电导和敏化的机械敏感性。值得注意的是，这三个插头被策略性地锁定在中心轴上，以协调三个门的门控。破坏闩锁会在Piezo1中感应出三个定量子导电状态，但不会在同形中。总之，我们建议Piezo利用一种优雅的即插即锁机制，通过可拼接的插塞门在物理上协调地对侧向门进行门控。
更新日期：2020-03-05
中文翻译：
门控机械灵敏压电通道的即插即用机制。
机械敏感的Piezo1和Piezo2通道将机械力转换为阳离子渗透。但是，它们的精确机械化和调节机制仍然难以捉摸。在这里，我们报告Piezo1利用配备有物理门的三个侧向离子导电门户进行协作门控和剪接调节。门户内衬的突变残基将Piezo1转换成阴离子选择性通道，说明了基于门户的阳离子渗透途径。有趣的是，门户在物理上被插件域阻塞，该插件域在Piezo1和Piezo2中都经历了可变的剪接。Piezo1同工型具有门户的局部开口，增大的单通道电导和敏化的机械敏感性。值得注意的是，这三个插头被策略性地锁定在中心轴上，以协调三个门的门控。破坏闩锁会在Piezo1中感应出三个定量子导电状态，但不会在同形中。总之，我们建议Piezo利用一种优雅的即插即锁机制，通过可拼接的插塞门在物理上协调地对侧向门进行门控。
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