Activation of TRPM7 Channels by Phospholipase C-coupled Receptor Agonists

TRPM7 is a ubiquitously expressed nonspecific cation channel that has been implicated in cellular Mg2+ homeostasis. We have recently shown that moderate overexpression of TRPM7 in neuroblastoma N1E-115 cells elevates cytosolic Ca2+ levels and enhances cell-matrix adhesion. Furthermore, activation of...

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Published in:The Journal of biological chemistry 2007-01, Vol.282 (1), p.232-239
Main Authors: Langeslag, Michiel, Clark, Kristopher, Moolenaar, Wouter H., van Leeuwen, Frank N., Jalink, Kees
Format: Article
Language:English
Subjects:
Bradykinin - metabolism
Calcium - metabolism
Cell Adhesion
Cell Line, Tumor
Fluorescence Resonance Energy Transfer
Humans
Lysophospholipids - chemistry
Magnesium - metabolism
Neuroblastoma - metabolism
Patch-Clamp Techniques
Protein Binding
Protein-Serine-Threonine Kinases
Signal Transduction
Thrombin - chemistry
TRPM Cation Channels - chemistry
Type C Phospholipases - chemistry
Type C Phospholipases - metabolism
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Summary:TRPM7 is a ubiquitously expressed nonspecific cation channel that has been implicated in cellular Mg2+ homeostasis. We have recently shown that moderate overexpression of TRPM7 in neuroblastoma N1E-115 cells elevates cytosolic Ca2+ levels and enhances cell-matrix adhesion. Furthermore, activation of TRPM7 by phospholipase C (PLC)-coupled receptor agonists caused a further increase in intracellular Ca2+ levels and augmented cell adhesion and spreading in a Ca2+-dependent manner (1). Regulation of the TRPM7 channel is not well understood, although it has been reported that PIP2 hydrolysis closes the channel. Here we have examined the regulation of TRPM7 by PLC-coupled receptor agonists such as bradykinin, lysophosphatidic acid, and thrombin. Using FRET assays for second messengers, we have shown that the TRPM7-dependent Ca2+ increase closely correlates with activation of PLC. Under non-invasive “perforated patch clamp” conditions, we have found similar activation of TRPM7 by PLC-coupled receptor agonists. Although we could confirm that, under whole-cell conditions, the TRPM7 currents were significantly inhibited following PLC activation, this PLC-dependent inhibition was only observed when [Mg2+]i was reduced below physiological levels. Thus, under physiological ionic conditions, TRPM7 currents were activated rather than inhibited by PLC-activating receptor agonists.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M605300200