TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

Kristopher Clark, Jeroen Middelbeek, Edwin Lasonder, Natalya G. Dulyaninova, Nick A. Morrice, Alexey G. Ryazanov, Anne R. Bresnick, Carl G. Figdor, Frank N. van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)


Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca2+- and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOH-termini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.

Original languageEnglish
Pages (from-to)790-803
Number of pages14
JournalJournal of Molecular Biology
Issue number4
Early online date4 May 2008
Publication statusPublished - 9 May 2008
Externally publishedYes


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