Abstract

Epidermal keratinocytes mediate touch sensation by detecting and encoding tactile information to sensory neurons. However, the specific mechanotransducers that enable keratinocytes to respond to mechanical stimulation are unknown. Here, we found that the mechanically-gated ion channel PIEZO1 is a key keratinocyte mechanotransducer. Keratinocyte expression of PIEZO1 is critical for normal sensory afferent firing and behavioral responses to mechanical stimuli in mice.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Alexander R Mikesell

    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Wauwatosa, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Olena Isaeva

    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. 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
  4. Katelyn E Sadler

    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:" 0000-0003-2078-3527
  5. 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.
  6. 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

National Institute of Neurological Disorders and Stroke (NS108278)

  • Cheryl L Stucky

Medical College of Wisconsin (Advancing a Healthier Wisconsin Endowment)

  • Cheryl L Stucky

National Institute of Neurological Disorders and Stroke (1F31NS125941-01)

  • Alexander R Mikesell

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

Ethics

Animal experimentation: Animal experimentation: All protocols were in accordance with National Institutes of Health guidelines and were approved by the Institutional Animal Care and Use Committee at the Medical College of Wisconsin (Milwaukee, WI; protocol #383).

Copyright

© 2022, Mikesell 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.

Metrics

  • 2,982
    views
  • 828
    downloads
  • 51
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Alexander R Mikesell
  2. Olena Isaeva
  3. Francie Moehring
  4. Katelyn E Sadler
  5. Anthony D Menzel
  6. Cheryl L Stucky
(2022)
Keratinocyte PIEZO1 modulates cutaneous mechanosensation
eLife 11:e65987.
https://doi.org/10.7554/eLife.65987

Share this article

https://doi.org/10.7554/eLife.65987

Further reading

    1. Cell Biology
    Yan Song, Linda J Fothergill ... Gene W Yeo
    Research Article

    Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.