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

Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction.

Author information

1
Sensory Cells and Circuits Section, National Center for Complementary and Integrative Health, 35 Convent Drive, Bethesda, MD 20892, USA.
2
Molecular Genetics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, 35 Convent Drive, Bethesda, MD 20892, USA.
3
Division of Library Services, Office of Research Services, NIH Library, NIH, 10 Center Drive, Bethesda, MD 20892, USA.
4
Unit on the Development of Neurodegeneration, National Institute of Child Health and Human Development, 35 Convent Drive, Bethesda, MD 20892, USA.
5
Sensory Cells and Circuits Section, National Center for Complementary and Integrative Health, 35 Convent Drive, Bethesda, MD 20892, USA. Electronic address: alexander.chesler@nih.gov.
6
Molecular Genetics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, 35 Convent Drive, Bethesda, MD 20892, USA. Electronic address: mark.hoon@nih.gov.

Abstract

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

PMID:
29212024
PMCID:
PMC5741189
DOI:
10.1016/j.celrep.2017.11.035
[Indexed for MEDLINE]
Free PMC Article

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