Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock
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.
Data availability
All data generated or analysed during this study are included in the manuscript
Article and author information
Author details
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
- Manuel Zimmer, University of Vienna, Austria
Publication history
- Preprint posted: November 17, 2021 (view preprint)
- Received: November 24, 2021
- Accepted: June 1, 2022
- Accepted Manuscript published: June 6, 2022 (version 1)
- Version of Record published: August 12, 2022 (version 2)
- Version of Record updated: August 22, 2022 (version 3)
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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