Cell Reports
Volume 21, Issue 10, 5 December 2017, Pages 2760-2771
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Article
Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

https://doi.org/10.1016/j.celrep.2017.11.035Get rights and content
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Highlights

  • Piezo2 undergoes alternative splicing

  • Sensory neurons express multiple Piezo2 variants; non-neuronal tissues express one

  • Different classes of touch neurons express different Piezo2 splice forms

  • Alternative splicing confers functional differences on Piezo2

Summary

Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, whereas non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli.

Keywords

Piezo
touch
sensation
ion-channel
splicing

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5

These authors contributed equally

6

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