Cargando…

TRPM7 is essential for Mg(2+) homeostasis in mammals

Mg(2+) is the second-most abundant cation in animal cells and is an essential cofactor in numerous enzymatic reactions. The molecular mechanisms controlling Mg(2+) balance in the organism are not well understood. In this study, we report identification of TRPM7, a bifunctional protein containing a p...

Descripción completa

Detalles Bibliográficos
Autores principales: Ryazanova, Lillia V., Rondon, Lusliany J., Zierler, Susanna, Hu, Zhixian, Galli, Joanna, Yamaguchi, Terry P., Mazur, Andrzej, Fleig, Andrea, Ryazanov, Alexey G.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060619/
https://www.ncbi.nlm.nih.gov/pubmed/21045827
http://dx.doi.org/10.1038/ncomms1108
Descripción
Sumario:Mg(2+) is the second-most abundant cation in animal cells and is an essential cofactor in numerous enzymatic reactions. The molecular mechanisms controlling Mg(2+) 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 Mg(2+) homeostasis in mammals. We generated TRPM7-deficient mice with the deletion of the kinase domain. Homozygous TRPM7(Δkinase) mice demonstrated early embryonic lethality, whereas heterozygous mice were viable, but developed signs of hypomagnesaemia and revealed a defect in intestinal Mg(2+) absorption. Cells derived from heterozygous TRPM7(Δkinase) mice demonstrated reduced TRPM7 currents that had increased sensitivity to the inhibition by Mg(2+). Embryonic stem cells lacking TRPM7 kinase domain displayed a proliferation arrest phenotype that can be rescued by Mg(2+) supplementation. Our results demonstrate that TRPM7 is essential for the control of cellular and whole body Mg(2+) homeostasis.