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Tuning piezo ion channels to detect molecular-scale movements relevant for fine touch

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Item Type:Article
Title:Tuning piezo ion channels to detect molecular-scale movements relevant for fine touch
Creators Name:Poole, K., Herget, R., Lapatsina, L., Ngo, H.D. and Lewin, G.R.
Abstract:In sensory neurons, mechanotransduction is sensitive, fast and requires mechanosensitive ion channels. Here we develop a new method to directly monitor mechanotransduction at defined regions of the cell-substrate interface. We show that molecular-scale (~13 nm) displacements are sufficient to gate mechanosensitive currents in mouse touch receptors. Using neurons from knockout mice, we show that displacement thresholds increase by one order of magnitude in the absence of stomatin-like protein 3 (STOML3). Piezo1 is the founding member of a class of mammalian stretch-activated ion channels, and we show that STOML3, but not other stomatin-domain proteins, brings the activation threshold for Piezo1 and Piezo2 currents down to ~10 nm. Structure-function experiments localize the Piezo modulatory activity of STOML3 to the stomatin domain, and higher-order scaffolds are a prerequisite for function. STOML3 is the first potent modulator of Piezo channels that tunes the sensitivity of mechanically gated channels to detect molecular-scale stimuli relevant for fine touch.
Keywords:Biophysics, Cellular Mechanotransduction, DNA Primers, HEK293 Cells, Immunoblotting, Immunoprecipitation, Inbred C57BL Mice, Ion Channels, Knockout Mice, Membrane Proteins, Neurological Models, Nerve Tissue Proteins, Nonparametric Statistics, Patch-Clamp Techniques, Physical Stimulation, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Scanning Electron Microscopy, Sensory Receptor Cells, Spinal Ganglia, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:3520
Date:24 March 2014
Official Publication:https://doi.org/10.1038/ncomms4520
PubMed:View item in PubMed

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