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

Chubanov, Vladimir, Ferioli, Silvia, Wisnowsky, Annika, Simmons, David G., Leitzinger, Christin, Einer, Claudia, Jonas, Wenke, Shymkiv, Yuriy, Bartsch, Harald, Braun, Attila, Akdogan, Banu, Mittermeier, Lorenz, Sytik, Ludmila, Torben, Friedrich, Jurinovic, Vindi, van der Vorst, Emiel P. C., Weber, Christian, Yildirim, Onder A., Sotlar, Karl, Schurmann, Annette, Zierler, Susanna, Zischka, Hans, Ryazanov, Alexey G. and Gudermann, Thomas (2016) Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival. eLife, 5 DECEMBER2016: . doi:10.7554/eLife.20914


Author Chubanov, Vladimir
Ferioli, Silvia
Wisnowsky, Annika
Simmons, David G.
Leitzinger, Christin
Einer, Claudia
Jonas, Wenke
Shymkiv, Yuriy
Bartsch, Harald
Braun, Attila
Akdogan, Banu
Mittermeier, Lorenz
Sytik, Ludmila
Torben, Friedrich
Jurinovic, Vindi
van der Vorst, Emiel P. C.
Weber, Christian
Yildirim, Onder A.
Sotlar, Karl
Schurmann, Annette
Zierler, Susanna
Zischka, Hans
Ryazanov, Alexey G.
Gudermann, Thomas
Title Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival
Journal name eLife   Check publisher's open access policy
ISSN 2050-084X
Publication date 2016-12-19
Year available 2016
Sub-type Article (original research)
DOI 10.7554/eLife.20914
Open Access Status DOI
Volume 5
Issue DECEMBER2016
Total pages 32
Place of publication Cambridge, United Kingdom
Publisher eLife Sciences Publications
Language eng
Subject 2800 Neuroscience
2700 Medicine
2400 Immunology and Microbiology
1300 Biochemistry, Genetics and Molecular Biology
Abstract Mg regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg 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 Mg 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 Mg 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 Mg balance by TRPM6 is crucial for prenatal development and survival to adulthood.
Formatted 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.
Keyword Biology
Life Sciences & Biomedicine - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID Marie-Curie Fellowship FP7-PEOPLE-2012-CIG
SFB1123-A1
TRP 152-P14
TRR 152-P15
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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