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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Phosphotransferases
Homeostasis
Transient Receptor Potential Channels
Peritoneal Macrophages
Locomotion
Ion Channels
Mutagenesis
Lysine
Mammals
Adenosine Triphosphate
Ions
Serum

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Kaitsuka, T., Katagiri, C., Beesetty, P., Nakamura, K., Hourani, S., Tomizawa, K., ... 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

Inactivation of TRPM7 kinase activity does not impair its channel function in mice. / Kaitsuka, Taku; Katagiri, Chiaki; Beesetty, Pavani; Nakamura, Kenji; Hourani, Siham; Tomizawa, Kazuhito; Kozak, J. Ashot; Matsushita, Masayuki.

In: Scientific Reports, Vol. 4, 5718, 17.07.2014.

Research output: Contribution to journalArticle

Kaitsuka, T, Katagiri, C, Beesetty, P, Nakamura, K, Hourani, S, Tomizawa, K, Kozak, JA & Matsushita, M 2014, 'Inactivation of TRPM7 kinase activity does not impair its channel function in mice', Scientific Reports, vol. 4, 5718. https://doi.org/10.1038/srep05718
Kaitsuka T, Katagiri C, Beesetty P, Nakamura K, Hourani S, Tomizawa K et al. Inactivation of TRPM7 kinase activity does not impair its channel function in mice. Scientific Reports. 2014 Jul 17;4. 5718. https://doi.org/10.1038/srep05718
Kaitsuka, Taku ; Katagiri, Chiaki ; Beesetty, Pavani ; Nakamura, Kenji ; Hourani, Siham ; Tomizawa, Kazuhito ; Kozak, J. Ashot ; Matsushita, Masayuki. / Inactivation of TRPM7 kinase activity does not impair its channel function in mice. In: Scientific Reports. 2014 ; Vol. 4.
@article{2be4bdffd69546759447aeac2f4a509a,
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.",
author = "Taku Kaitsuka and Chiaki Katagiri and Pavani Beesetty and Kenji Nakamura and Siham Hourani and Kazuhito Tomizawa and Kozak, {J. Ashot} and Masayuki Matsushita",
year = "2014",
month = "7",
day = "17",
doi = "10.1038/srep05718",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Inactivation of TRPM7 kinase activity does not impair its channel function in mice

AU - Kaitsuka, Taku

AU - Katagiri, Chiaki

AU - Beesetty, Pavani

AU - Nakamura, Kenji

AU - Hourani, Siham

AU - Tomizawa, Kazuhito

AU - Kozak, J. Ashot

AU - Matsushita, Masayuki

PY - 2014/7/17

Y1 - 2014/7/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84904620657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904620657&partnerID=8YFLogxK

U2 - 10.1038/srep05718

DO - 10.1038/srep05718

M3 - Article

C2 - 25030553

AN - SCOPUS:84904620657

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 5718

ER -