TRPM7 is essential for Mg2+ homeostasis in mammals
Abstract
Mg2+ is the second-most abundant cation in animal cells and is an essential cofactor in numerous enzymatic reactions. The molecular mechanisms controlling Mg2+ balance in the organism are not well understood. In this study, we report identification of TRPM7, a bifunctional protein containing a protein kinase fused to an ion channel, as a key regulator of whole body Mg2+ homeostasis in mammals. We generated TRPM7-deficient mice with the deletion of the kinase domain. Homozygous TRPM7Δkinase mice demonstrated early embryonic lethality, whereas heterozygous mice were viable, but developed signs of hypomagnesaemia and revealed a defect in intestinal Mg2+ absorption. Cells derived from heterozygous TRPM7Δkinase mice demonstrated reduced TRPM7 currents that had increased sensitivity to the inhibition by Mg2+. Embryonic stem cells lacking TRPM7 kinase domain displayed a proliferation arrest phenotype that can be rescued by Mg2+ supplementation. Our results demonstrate that TRPM7 is essential for the control of cellular and whole body Mg2+ homeostasis.
- Publication:
-
Nature Communications
- Pub Date:
- November 2010
- DOI:
- 10.1038/ncomms1108
- Bibcode:
- 2010NatCo...1..109R