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TRPM7 kinase activity regulates murine mast cell degranulation
Author(s) -
Zierler Susanna,
SumozaToledo Adriana,
Suzuki Sayuri,
Dúill Fionán Ó,
Ryazanova Lillia V.,
Penner Reinhold,
Ryazanov Alexey G.,
Fleig Andrea
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp271564
Subject(s) - degranulation , mast cell , microbiology and biotechnology , mast (botany) , chemistry , immunology , biology , biochemistry , receptor
Key points The Mg 2+ and Ca 2+ conducting transient receptor potential melastatin 7 (TRPM7) channel–enzyme (chanzyme) has been implicated in immune cell function. Mice heterozygous for a TRPM7 kinase deletion are hyperallergic, while mice with a single point mutation at amino acid 1648, silencing kinase activity, are not. As mast cell mediators trigger allergic reactions, we here determine the function of TRPM7 in mast cell degranulation and histamine release. Our data establish that TRPM7 kinase activity regulates mast cell degranulation and release of histamine independently of TRPM7 channel function. Our findings suggest a regulatory role of TRPM7 kinase activity on intracellular Ca 2+ and extracellular Mg 2+ sensitivity of mast cell degranulation.Abstract Transient receptor potential melastatin 7 (TRPM7) is a divalent ion channel with a C‐terminally located α‐kinase. Mice heterozygous for a TRPM7 kinase deletion (TRPM7 +/∆K ) are hypomagnesaemic and hyperallergic. In contrast, mice carrying a single point mutation at amino acid 1648, which silences TRPM7 kinase activity (TRPM7 KR ), are not hyperallergic and are resistant to systemic magnesium (Mg 2+ ) deprivation. Since allergic reactions are triggered by mast cell‐mediated histamine release, we investigated the function of TRPM7 on mast cell degranulation and histamine release using wild‐type (TRPM7 +/+ ), TRPM7 +/∆K and TRPM7 KR mice. We found that degranulation and histamine release proceeded independently of TRPM7 channel function. Furthermore, extracellular Mg 2+ assured unperturbed IgE‐DNP‐dependent exocytosis, independently of TRPM7. However, impairment of TRPM7 kinase function suppressed IgE‐DNP‐dependent exocytosis, slowed the cellular degranulation rate, and diminished the sensitivity to intracellular calcium (Ca 2+ ) in G protein‐induced exocytosis. In addition, G protein‐coupled receptor (GPCR) stimulation revealed strong suppression of histamine release, whereas removal of extracellular Mg 2+ caused the phenotype to revert. We conclude that the TRPM7 kinase activity regulates murine mast cell degranulation by changing its sensitivity to intracellular Ca 2+ and affecting granular mobility and/or histamine contents.