Piezo2 is the major transducer of mechanical forces for touch sensation in mice

Sanjeev S. Ranade, Seung Hyun Woo, Adrienne E. Dubin, Rabih A. Moshourab, Christiane Wetzel, Matt Petrus, Jayanti Mathur, Valérie Bégay, Bertrand Coste, James Mainquist, A. J. Wilson, Allain G. Francisco, Kritika Reddy, Zhaozhu Qiu, John N. Wood, Gary R. Lewin, Ardem Patapoutian

Research output: Contribution to journalArticle

Abstract

The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.

Original languageEnglish (US)
Pages (from-to)121-125
Number of pages5
JournalNature
Volume516
Issue number729
DOIs
StatePublished - Dec 4 2014
Externally publishedYes

Fingerprint

Touch
Transducers
Merkel Cells
Mechanoreceptors
Sensory Receptor Cells
Ion Channels
Spinal Ganglia
Skin
Phenotype
Neurites
Knockout Mice
Vertebrates
Cations
Mammals
Pain

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Ranade, S. S., Woo, S. H., Dubin, A. E., Moshourab, R. A., Wetzel, C., Petrus, M., ... Patapoutian, A. (2014). Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature, 516(729), 121-125. https://doi.org/10.1038/nature13980

Piezo2 is the major transducer of mechanical forces for touch sensation in mice. / Ranade, Sanjeev S.; Woo, Seung Hyun; Dubin, Adrienne E.; Moshourab, Rabih A.; Wetzel, Christiane; Petrus, Matt; Mathur, Jayanti; Bégay, Valérie; Coste, Bertrand; Mainquist, James; Wilson, A. J.; Francisco, Allain G.; Reddy, Kritika; Qiu, Zhaozhu; Wood, John N.; Lewin, Gary R.; Patapoutian, Ardem.

In: Nature, Vol. 516, No. 729, 04.12.2014, p. 121-125.

Research output: Contribution to journalArticle

Ranade, SS, Woo, SH, Dubin, AE, Moshourab, RA, Wetzel, C, Petrus, M, Mathur, J, Bégay, V, Coste, B, Mainquist, J, Wilson, AJ, Francisco, AG, Reddy, K, Qiu, Z, Wood, JN, Lewin, GR & Patapoutian, A 2014, 'Piezo2 is the major transducer of mechanical forces for touch sensation in mice', Nature, vol. 516, no. 729, pp. 121-125. https://doi.org/10.1038/nature13980
Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature. 2014 Dec 4;516(729):121-125. https://doi.org/10.1038/nature13980
Ranade, Sanjeev S. ; Woo, Seung Hyun ; Dubin, Adrienne E. ; Moshourab, Rabih A. ; Wetzel, Christiane ; Petrus, Matt ; Mathur, Jayanti ; Bégay, Valérie ; Coste, Bertrand ; Mainquist, James ; Wilson, A. J. ; Francisco, Allain G. ; Reddy, Kritika ; Qiu, Zhaozhu ; Wood, John N. ; Lewin, Gary R. ; Patapoutian, Ardem. / Piezo2 is the major transducer of mechanical forces for touch sensation in mice. In: Nature. 2014 ; Vol. 516, No. 729. pp. 121-125.
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