Inactivation of TRPM7 kinase activity does not impair its channel function in mice

Sci Rep. 2014 Jul 17;4:5718. doi: 10.1038/srep05718.

Abstract

Transient receptor potential (TRP) family channels are involved in sensory pathways and respond to various environmental stimuli. Among the members of this family, TRPM7 is a unique fusion of an ion channel and a C-terminus kinase domain that is highly expressed in immune cells. TRPM7 serves as a key molecule governing cellular Mg(2+) homeostasis in mammals since its channel pore is permeable to Mg(2+) ions and can act as a Mg(2+) influx pathway. However, mechanistic links between its kinase activity and channel function have remained uncertain. In this study, we generated kinase inactive knock-in mutant mice by mutagenesis of a key lysine residue involved in Mg(2+)-ATP binding. These mutant mice were normal in development and general locomotor activity. In peritoneal macrophages isolated from adult animals the basal activity of TRPM7 channels prior to cytoplasmic Mg(2+) depletion was significantly potentiated, while maximal current densities measured after Mg(2+) depletion were unchanged in the absence of detectable kinase function. Serum total Ca(2+) and Mg(2+) levels were not significantly altered in kinase-inactive mutant mice. Our findings suggest that abolishing TRPM7 kinase activity does not impair its channel activity and kinase activity is not essential for regulation of mammalian Mg(2+) homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Gene Knock-In Techniques
  • Homeostasis
  • Macrophages / metabolism
  • Magnesium / metabolism
  • Male
  • Membrane Potentials
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Patch-Clamp Techniques
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism

Substances

  • TRPM Cation Channels
  • Trpm7 protein, mouse
  • Magnesium