TRPM7, a novel regulator of actomyosin contractility and cell adhesion

Kristopher Clark, Michiel Langeslag, Bart van Leeuwen, Leonie Ran, Alexey G Ryazanov, Carl G Figdor, Wouter H Moolenaar, Kees Jalink, Frank N van Leeuwen

Research output: Contribution to journalArticlepeer-review

Abstract

Actomyosin contractility regulates various cell biological processes including cytokinesis, adhesion and migration. While in lower eukaryotes, alpha-kinases control actomyosin relaxation, a similar role for mammalian alpha-kinases has yet to be established. Here, we examined whether TRPM7, a cation channel fused to an alpha-kinase, can affect actomyosin function. We demonstrate that activation of TRPM7 by bradykinin leads to a Ca(2+)- and kinase-dependent interaction with the actomyosin cytoskeleton. Moreover, TRPM7 phosphorylates the myosin IIA heavy chain. Accordingly, low overexpression of TRPM7 increases intracellular Ca2+ levels accompanied by cell spreading, adhesion and the formation of focal adhesions. Activation of TRPM7 induces the transformation of these focal adhesions into podosomes by a kinase-dependent mechanism, an effect that can be mimicked by pharmacological inhibition of myosin II. Collectively, our results demonstrate that regulation of cell adhesion by TRPM7 is the combined effect of kinase-dependent and -independent pathways on actomyosin contractility.

Original languageEnglish
Pages (from-to)290-301
Number of pages12
JournalThe EMBO journal
Volume25
Issue number2
DOIs
Publication statusPublished - 25 Jan 2006
Externally publishedYes

Keywords

  • Actomyosin/metabolism
  • Animals
  • Calcium/metabolism
  • Cell Adhesion/physiology
  • Cell Line
  • Cytoskeleton/metabolism
  • Humans
  • Immunoprecipitation
  • Mice
  • Microscopy, Fluorescence
  • Nonmuscle Myosin Type IIA/metabolism
  • Phosphorylation
  • Phosphotransferases/metabolism
  • Protein Serine-Threonine Kinases
  • TRPM Cation Channels/metabolism

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