1. Structural Biology and Molecular Biophysics
  2. Human Biology and Medicine
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Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

  1. Vladimir Chubanov  Is a corresponding author
  2. Silvia Ferioli
  3. Annika Wisnowsky
  4. David G Simmons
  5. Christin Leitzinger
  6. Claudia Einer
  7. Wenke Jonas
  8. Yuriy Shymkiv
  9. Harald Bartsch
  10. Attila Braun
  11. Banu Akdogan
  12. Lorenz Mittermeier
  13. Ludmila Sytik
  14. Friedrich Torben
  15. Vindi Jurinovic
  16. Emiel PC van der Vorst
  17. Christian Weber
  18. Önder A Yildirim
  19. Karl Sotlar
  20. Annette Schürmann
  21. Susanna Zierler
  22. Hans Zischka
  23. Alexey G Ryazanov
  24. Thomas Gudermann  Is a corresponding author
  1. Ludwig Maximilian University of Munich, Germany
  2. The University of Queensland, Australia
  3. Helmholtz Zentrum Munich, Germany
  4. German Institute of Human Nutrition, Germany
  5. Princeton Institute of Life Sciences, United States
  6. University of Würzburg, Germany
  7. LMU Munich, Germany
  8. Paracelsus Medical University, Austria
Research Article
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Cite this article as: eLife 2016;5:e20914 doi: 10.7554/eLife.20914

Abstract

Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.

Article and author information

Author details

  1. Vladimir Chubanov

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    For correspondence
    vladimir.chubanov@lrz.uni-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6042-4193
  2. Silvia Ferioli

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Annika Wisnowsky

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. David G Simmons

    School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4115-9371
  5. Christin Leitzinger

    Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Claudia Einer

    Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Wenke Jonas

    Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Yuriy Shymkiv

    Princeton Institute of Life Sciences, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Harald Bartsch

    Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Attila Braun

    Department of Vascular Medicine, University Hospital and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Banu Akdogan

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Lorenz Mittermeier

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Ludmila Sytik

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Friedrich Torben

    Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum Munich, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  15. Vindi Jurinovic

    IBE, LMU Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  16. Emiel PC van der Vorst

    Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  17. Christian Weber

    Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  18. Önder A Yildirim

    Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  19. Karl Sotlar

    Institute of Pathology, Paracelsus Medical University, Salzburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  20. Annette Schürmann

    Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany
    Competing interests
    The authors declare that no competing interests exist.
  21. Susanna Zierler

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4684-0385
  22. Hans Zischka

    Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  23. Alexey G Ryazanov

    Princeton Institute of Life Sciences, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  24. Thomas Gudermann

    Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
    For correspondence
    thomas.gudermann@lrz.uni-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.

Funding

Deutsche Forschungsgemeinschaft (TRR 152-P15)

  • Vladimir Chubanov

Deutsche Forschungsgemeinschaft (TRP 152-P15)

  • Thomas Gudermann

Deutsche Forschungsgemeinschaft (TRP 152-P14)

  • Susanna Zierler

Deutsche Forschungsgemeinschaft (SFB1123-A1)

  • Emiel PC van der Vorst
  • Christian Weber

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

Ethics

Animal experimentation: Experiments involving animals were done in accordance with the EU Animal Welfare Act and were approved by the local councils on animal care (permit No 55.2-1-54-2532-134-13 from Government of Oberbayern, Germany, and permit No 2347-15-2014 from State Ministry of Brandenburg, Germany).

Reviewing Editor

  1. Richard S Lewis, Stanford University School of Medicine, United States

Publication history

  1. Received: August 25, 2016
  2. Accepted: December 13, 2016
  3. Accepted Manuscript published: December 19, 2016 (version 1)
  4. Version of Record published: January 6, 2017 (version 2)

Copyright

© 2016, Chubanov 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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