Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock

  1. Eva Kaulich
  2. Trae Carroll
  3. Brian Ackley
  4. Yi-Quan Tang
  5. Iris Hardege
  6. Keith Nehrke
  7. William R Schafer  Is a corresponding author
  8. Denise S Walker  Is a corresponding author
  1. MRC Laboratory of Molecular Biology, United Kingdom
  2. University of Rochester, United States
  3. University of Kansas, United States
  4. Fudan University, China

Abstract

Biological clocks are fundamental to an organism’s health, controlling periodicity of behaviour and metabolism. Here, we identify two acid-sensing ion channels, with very different proton sensing properties, and describe their role in an ultradian clock, the defecation motor program (DMP) of the nematode Caenorhabditis elegans. An ACD-5-containing channel, on the apical membrane of the intestinal epithelium, is essential for maintenance of luminal acidity, and thus the rhythmic oscillations in lumen pH. In contrast, the second channel, composed of FLR-1, ACD-3 and/or DEL-5, located on the basolateral membrane, controls the intracellular Ca2+ wave and forms a core component of the master oscillator that controls timing and rhythmicity of the DMP. flr-1 and acd-3/del-5 mutants show severe developmental and metabolic defects. We thus directly link the proton-sensing properties of these channels to their physiological roles in pH regulation and Ca2+ signalling, the generation of an ultradian oscillator, and its metabolic consequences.

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All data generated or analysed during this study are included in the manuscript

Article and author information

Author details

  1. Eva Kaulich

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0868-3702
  2. Trae Carroll

    Department of Pathology and Lab Medicine, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Brian Ackley

    Department of Molecular Biosciences, University of Kansas, Lawrence, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1257-2407
  4. Yi-Quan Tang

    Institutes of Brain Science, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Iris Hardege

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Keith Nehrke

    Department of Medicine, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. William R Schafer

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    For correspondence
    wschafer@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6676-8034
  8. Denise S Walker

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    For correspondence
    dwalker@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1534-1679

Funding

Medical Research Council (MC-A023-5PB91)

  • William R Schafer

Wellcome Trust (WT103784MA)

  • William R Schafer

KU Center for Chemical Biology of Infectious Diseases (P20GM113117)

  • Brian Ackley

National Institutes of Health (R01AG067617)

  • Keith Nehrke

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

Reviewing Editor

  1. Manuel Zimmer, University of Vienna, Austria

Publication history

  1. Received: November 24, 2021
  2. Accepted: June 1, 2022
  3. Accepted Manuscript published: June 6, 2022 (version 1)

Copyright

© 2022, Kaulich 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. Eva Kaulich
  2. Trae Carroll
  3. Brian Ackley
  4. Yi-Quan Tang
  5. Iris Hardege
  6. Keith Nehrke
  7. William R Schafer
  8. Denise S Walker
(2022)
Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock
eLife 11:e75837.
https://doi.org/10.7554/eLife.75837

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