Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction
Marcin Szczot,
Leah A. Pogorzala,
Hans Jürgen Solinski,
Lynn Young,
Philina Yee,
Claire E. Le Pichon,
Alexander T. Chesler,
Mark A. Hoon
Affiliations
Marcin Szczot
Sensory Cells and Circuits Section, National Center for Complementary and Integrative Health, 35 Convent Drive, Bethesda, MD 20892, USA
Leah A. Pogorzala
Molecular Genetics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, 35 Convent Drive, Bethesda, MD 20892, USA
Hans Jürgen Solinski
Molecular Genetics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, 35 Convent Drive, Bethesda, MD 20892, USA
Lynn Young
Division of Library Services, Office of Research Services, NIH Library, NIH, 10 Center Drive, Bethesda, MD 20892, USA
Philina Yee
Sensory Cells and Circuits Section, National Center for Complementary and Integrative Health, 35 Convent Drive, Bethesda, MD 20892, USA
Claire E. Le Pichon
Unit on the Development of Neurodegeneration, National Institute of Child Health and Human Development, 35 Convent Drive, Bethesda, MD 20892, USA
Alexander T. Chesler
Sensory Cells and Circuits Section, National Center for Complementary and Integrative Health, 35 Convent Drive, Bethesda, MD 20892, USA; Corresponding author
Mark A. Hoon
Molecular Genetics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, 35 Convent Drive, Bethesda, MD 20892, USA; Corresponding author
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. : Szczot et al. find that the mechanoreceptor Piezo2 is extensively alternatively spliced, generating multiple distinct isoforms. Their findings indicate that these splice products have specific tissue and cell type expression patterns and exhibit differences in receptor properties. Keywords: Piezo, touch, sensation, ion-channel, splicing
