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TRPM7 is essential for Mg2+ homeostasis in mammals

  1. Author:
    Ryazanova, L. V.
    Rondon, L. J.
    Zierler, S.
    Hu, Z. X.
    Galli, J.
    Yamaguchi, T. P.
    Mazur, A.
    Fleig, A.
    Ryazanov, A. G.

  2. Author Address

    [Ryazanova, Lillia V.; Hu, Zhixian; Ryazanov, Alexey G.] Univ Med & Dent New Jersey, Dept Pharmacol, RW Johnson Med Sch, Piscataway, NJ 08854 USA. [Rondon, Lusliany J.; Galli, Joanna; Mazur, Andrzej] Univ Auvergne, UNH, INRA, UMR 1019,CRNH Auvergne, F-63000 Clermont Ferrand, France. [Rondon, Lusliany J.; Galli, Joanna; Mazur, Andrzej] Univ Auvergne, Clermont Univ, Unite Nutr Humaine, F-63000 Clermont Ferrand, France. [Zierler, Susanna; Fleig, Andrea] Univ Hawaii, Queens Ctr Biomed Res, Lab Cell & Mol Signaling, Queens Ctr Biomed Res, Honolulu, HI 96813 USA. [Zierler, Susanna; Fleig, Andrea] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96813 USA. [Galli, Joanna] Wroclaw Univ Environm & Life Sci, Fac Vet Med, PL-50375 Wroclaw, Poland. [Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH Frederick, Frederick, MD 21702 USA.;Ryazanov, AG, Univ Med & Dent New Jersey, Dept Pharmacol, RW Johnson Med Sch, 675 Hoes Lane, Piscataway, NJ 08854 USA.;ryazanag@umdnj.edu
    1. Year: 2010
    2. Date: Nov
  2. Journal: Nature Communications
    1. 1
    2. Pages: 9
  4. Type of Article: Article
  5. Article Number: 109
  6. ISSN: 2041-1723
  1. 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 TRPM7(Delta kinase) 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 TRPM7(Delta kinase) 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.

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  2. DOI: 10.1038/ncomms1108
  3. View record in Web of Science®
  4. WOS: 000288224800007

Library Notes

  1. Fiscal Year: FY2010-2011
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