EMBO J. 2006 Jan 25;25(2):290-301. Epub 2006 Jan 12.
TRPM7, a novel regulator of actomyosin contractility and cell adhesion.
Clark, K., Langeslag, M., van Leeuwen, B., Ran, L., Ryazanov, A. G., Figdor, C. G., Moolenaar, W. H., Jalink, K., van Leeuwen, F. N.,
["Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands."]
["Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands."]
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.
PMID: 16407977

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Screening
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPM7 |
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Ƣ-actin | Inference | Prediction | 16407977 | |||||
TRPM7 |
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Myosin-HIIA | Inference | Prediction | 16407977 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vivo validation
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPM7 |
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Ƣ-actin | Co-immunofluorescence staining | N1E-115 neuroblastoma cell | Mouse | Full-length | Not used | 16407977 | ||
TRPM7 |
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Ƣ-actin | Co-immunoprecipitation | N1E-115 neuroblastoma cell | Mouse | Full-length | Not used | 16407977 | ||
TRPM7 |
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Myosin-HIIA | Co-immunoprecipitation | N1E-115 neuroblastoma cell | Mouse | Full-length | Not used | 16407977 | ||
TRPM7 |
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Myosin-HIIA | Co-immunoprecipitation | PC12 | 16407977 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Characterization
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Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPM7 |
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Myosin-HIIA | Co-immunoprecipitation | Mouse | 1158-1864 | Mouse | 1795-1960 | 16407977 |
(
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
