title: TRPM7, a novel regulator of actomyosin contractility and cell adhesion.
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.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Clark
authors.forename: Michiel
authors.initials: M
authors.lastname: Langeslag
authors.forename: Bart
authors.initials: B
authors.lastname: van Leeuwen
authors.forename: Leonie
authors.initials: L
authors.lastname: Ran
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Ryazanov
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Moolenaar
authors.forename: Kees
authors.initials: K
authors.lastname: Jalink
authors.forename: Frank N
authors.initials: FN
authors.lastname: van Leeuwen
mesh_terms: D000205:Actomyosin / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; D000205:Actomyosin; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D024507:Nonmuscle Myosin Type IIA; D002118:Calcium