Abstract

The first point of our body's contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions.

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Author details

  1. Francie Moehring

    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0071-5685
  2. Ashley M Cowie

    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Anthony D Menzel

    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Andy D Weyer

    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael Grzybowski

    Department of Physiology, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Thiago Arzua

    Department of Physiology, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Aron M Geurts

    Department of Physiology, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Oleg Palygin

    Department of Physiology, Medical College of Wisconsin, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3680-5527
  9. Cheryl L Stucky

    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States
    For correspondence
    cstucky@mcw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4966-6594

Funding

National Institute of Neurological Disorders and Stroke (NS040538)

  • Cheryl L Stucky

National Institute of Neurological Disorders and Stroke (NS070711)

  • Cheryl L Stucky

Advancing a Healthier Wisconsin Endowment

  • Cheryl L Stucky

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All of the animal procedures strictly adhered to the NIH Guide for the Care and Use of Laboratory animals, and were performed in accordance with the Institutional Animal Care and Use Committee at the Medical College of Wisconsin (approval #: 0383).

Copyright

© 2018, Moehring et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Francie Moehring
  2. Ashley M Cowie
  3. Anthony D Menzel
  4. Andy D Weyer
  5. Michael Grzybowski
  6. Thiago Arzua
  7. Aron M Geurts
  8. Oleg Palygin
  9. Cheryl L Stucky
(2018)
Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling
eLife 7:e31684.
https://doi.org/10.7554/eLife.31684

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https://doi.org/10.7554/eLife.31684