Reevaluation of Piezo1 as a gut RNA sensor

  1. Alec R Nickolls
  2. Gabrielle S O'Brien
  3. Sarah Shnayder
  4. Yunxiao Zhang
  5. Maximilian Nagel
  6. Ardem Patapoutian
  7. Alexander Theodore Chesler  Is a corresponding author
  1. National Institutes of Health, United States
  2. Howard Hughes Medical Institute, Scripps Research Institute, United States

Abstract

Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent findings point to a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observe that fecal extracts and ssRNA can stimulate calcium influx in certain cell lines, this response is independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA show similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data have been deposited on the GEO website.

The following data sets were generated

Article and author information

Author details

  1. Alec R Nickolls

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  2. Gabrielle S O'Brien

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  3. Sarah Shnayder

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  4. Yunxiao Zhang

    Department of Neuroscience, Howard Hughes Medical Institute, Scripps Research Institute, La Jolla, United States
    Competing interests
    No competing interests declared.
  5. Maximilian Nagel

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  6. Ardem Patapoutian

    Department of Neuroscience, Howard Hughes Medical Institute, Scripps Research Institute, La Jolla, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0726-7034
  7. Alexander Theodore Chesler

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    For correspondence
    alexander.chesler@nih.gov
    Competing interests
    Alexander Theodore Chesler, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3131-0728

Funding

National Center for Complementary and Integrative Health (Intramural funds)

  • Alexander Theodore Chesler

National Institute of Neurological Disorders and Stroke (Intramural funds)

  • Alexander Theodore Chesler

National Center for Advancing Translational Sciences (Intramural funds)

  • Alexander Theodore Chesler

Howard Hughes Medical Institute

  • Ardem Patapoutian

National Institutes of Health (R35 NS105067)

  • Ardem Patapoutian

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

Reviewing Editor

  1. Jon T Sack, University of California Davis School of Medicine, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#1365) of the NINDS-IRP.

Version history

  1. Received: September 8, 2022
  2. Preprint posted: September 24, 2022 (view preprint)
  3. Accepted: November 15, 2022
  4. Accepted Manuscript published: November 16, 2022 (version 1)
  5. Version of Record published: November 24, 2022 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Alec R Nickolls
  2. Gabrielle S O'Brien
  3. Sarah Shnayder
  4. Yunxiao Zhang
  5. Maximilian Nagel
  6. Ardem Patapoutian
  7. Alexander Theodore Chesler
(2022)
Reevaluation of Piezo1 as a gut RNA sensor
eLife 11:e83346.
https://doi.org/10.7554/eLife.83346

Share this article

https://doi.org/10.7554/eLife.83346

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