Activation of TRPM7 channels by phospholipase C-coupled receptor agonists

Michiel Langeslag, Kristopher Clark, Wouter H Moolenaar, Frank N van Leeuwen, Kees Jalink

Research output: Contribution to journalArticlepeer-review

Abstract

TRPM7 is a ubiquitously expressed nonspecific cation channel that has been implicated in cellular Mg(2+) homeostasis. We have recently shown that moderate overexpression of TRPM7 in neuroblastoma N1E-115 cells elevates cytosolic Ca(2+) levels and enhances cell-matrix adhesion. Furthermore, activation of TRPM7 by phospholipase C (PLC)-coupled receptor agonists caused a further increase in intracellular Ca(2+) levels and augmented cell adhesion and spreading in a Ca(2+)-dependent manner (1). Regulation of the TRPM7 channel is not well understood, although it has been reported that PIP(2) 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 Ca(2+) 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 [Mg(2+)](i) was reduced below physiological levels. Thus, under physiological ionic conditions, TRPM7 currents were activated rather than inhibited by PLC-activating receptor agonists.

Original languageEnglish
Pages (from-to)232-9
Number of pages8
JournalThe Journal of biological chemistry
Volume282
Issue number1
DOIs
Publication statusPublished - 5 Jan 2007
Externally publishedYes

Keywords

  • 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
  • TRPM Cation Channels/chemistry
  • Thrombin/chemistry
  • Type C Phospholipases/chemistry

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