Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

Cell Rep. 2017 Dec 5;21(10):2760-2771. doi: 10.1016/j.celrep.2017.11.035.


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; ion-channel; sensation; splicing; touch.

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Electrophysiology
  • Female
  • HEK293 Cells
  • Humans
  • In Situ Hybridization
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Male
  • Mechanotransduction, Cellular / genetics
  • Mechanotransduction, Cellular / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splicing / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Ion Channels
  • PIEZO2 protein, human
  • Piezo2 protein, mouse
  • Protein Isoforms