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Piezo2 is the principal mechanotransduction channel for proprioception

Nature Neuroscience volume 18, pages 17561762 (2015) | Download Citation

Abstract

Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.

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Acknowledgements

We thank B. Coste (Aix Marseille Université) for suggestions and H.U. Zeilhofer (University of Zurich) and R. Seal (University of Pittsburgh) for providing HoxB8-Cre mice. This work was supported by the Howard Hughes Medical Institute and US National Institutes of Health grant R01DE022358.

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Affiliations

  1. Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.

    • Seung-Hyun Woo
    • , Viktor Lukacs
    • , Allain Francisco
    •  & Ardem Patapoutian
  2. Howard Hughes Medical Institute, Department of Neuroscience, Columbia University, New York, New York, USA.

    • Joriene C de Nooij
    •  & Thomas M Jessell
  3. Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.

    • Joriene C de Nooij
    •  & Thomas M Jessell
  4. Department of Biological Sciences, San José State University, San Jose, California, USA.

    • Dasha Zaytseva
    • , Connor R Criddle
    •  & Katherine A Wilkinson

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Contributions

V.L. performed whole-cell electrophysiology in isolated DRG neurons. J.C.d.N. characterized Piezo2 cKO muscles in the laboratory of T.M.J. D.Z., C.R.C. and K.A.W. contributed to data collection and analyses for ex vivo muscle-nerve recordings in the laboratory of K.A.W. A.F. isolated DRG neurons for whole-cell electrophysiology. S.-H.W. contributed to all of the other experiments. S.-H.W., V.L., K.A.W. and A.P. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ardem Patapoutian.

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https://doi.org/10.1038/nn.4162

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