PubMed 25030553

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPM , TRPM7

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

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

Journal, date & volume: Sci Rep, 2014 , 4, 5718

PubMed link:

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.