Neuron
Volume 89, Issue 6, 16 March 2016, Pages 1248-1263
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Article
Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels

https://doi.org/10.1016/j.neuron.2016.01.046Get rights and content
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Highlights

  • The last-two-TM-containing region (residues 2,189–2,547) of mPiezo1 encodes the pore

  • The last putative TM forms the pore-lining helix

  • Key acidic residues located in the pore region determine pore properties

  • The non-pore-containing region is sufficient for mechanotransduction

Summary

Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively.

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