Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

Vladimir Chubanov, Silvia Ferioli, Annika Wisnowsky, David G. Simmons, Christin Leitzinger, Claudia Einer, Wenke Jonas, Yuriy Shymkiv, Harald Bartsch, Attila Braun, Banu Akdogan, Lorenz Mittermeier, Ludmila Sytik, Friedrich Torben, Vindi Jurinovic, Emiel P.C. van der Vorst, Christian Weber, Önder A. Yildirim, Karl Sotlar, Annette SchürmannSusanna Zierler, Hans Zischka, Alexey G. Ryazanov, Thomas Gudermann

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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 a 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.

Original languageEnglish (US)
Article numbere20914
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - Dec 19 2016

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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