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

Taku Kaitsuka, Chiaki Katagiri, Pavani Beesetty, Kenji Nakamura, Siham Hourani, Kazuhito Tomizawa, J. Ashot Kozak, Masayuki Matsushita

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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.

Original languageEnglish
Article number5718
JournalScientific reports
Volume4
DOIs
Publication statusPublished - Jul 17 2014

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Cite this

Kaitsuka, T., Katagiri, C., Beesetty, P., Nakamura, K., Hourani, S., Tomizawa, K., Kozak, J. A., & Matsushita, M. (2014). Inactivation of TRPM7 kinase activity does not impair its channel function in mice. Scientific reports, 4, [5718]. https://doi.org/10.1038/srep05718