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Chubanov, V.* ; Ferioli, S.* ; Wisnowsky, A.* ; Simmons, D.G.* ; Leitzinger, C. ; Einer, C. ; Jonas, W.* ; Shymkiv, Y.* ; Bartsch, H.* ; Braun, A.* ; Akdogan, B.* ; Mittermeier, L.* ; Sytik, L.* ; Torben, F. ; Jurinovic, V.* ; van der Vorst, E.P.C.* ; Weber, C.* ; Yildirim, A.Ö. ; Sotlar, K.* ; Schürmann, A.* ; Zierler, S.* ; Zischka, H. ; Ryazanov, A.G.* ; Gudermann, T.*

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

eLife 5:e29014 (2016)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cellular Mg2+ Homeostasis; Field Mass-spectrometry; Secondary Hypocalcemia; Primary Hypomagnesemia; Embryonic-development; Somatotroph Axis; Human-cells; Rat-liver; Mice; Growth

ISSN (print) / ISBN 2050-084X

e-ISSN 2050-084X

Journal eLife

Quellenangaben Volume: 5, Article Number: e29014

Publisher eLife Sciences Publications

Publishing Place Cambridge

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)
Institute for Allergy Research (IAF)
Molekulare Endokrinologie und Metabolismus (MEM)