title: Inactivation of TRPM7 kinase activity does not impair its channel function in mice.
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.
authors.affiliation: 1] Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan [2] Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan [3].
authors.forename: Taku
authors.initials: T
authors.lastname: Kaitsuka
authors.affiliation: 1] Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan [2] Department of Molecular and Cellular Physiology Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan [3].
authors.forename: Chiaki
authors.initials: C
authors.lastname: Katagiri
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435, USA.
authors.forename: Pavani
authors.initials: P
authors.lastname: Beesetty
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435, USA.
authors.forename: Siham
authors.initials: S
authors.lastname: Hourani
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435, USA.
authors.forename: J Ashot
authors.initials: JA
authors.lastname: Kozak
authors.affiliation: 1] Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan [2] Department of Molecular and Cellular Physiology Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D055879:Gene Knock-In Techniques; D006706:Homeostasis; D008264:Macrophages / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse; D008274:Magnesium