Related Experiment Video

Updated: Jul 6, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation

Kristopher Clark1, Jeroen Middelbeek, Edwin Lasonder

  • 1Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Journal of Molecular Biology
|April 9, 2008
PubMed

Insights

The mammalian kinase TRPM7 regulates myosin IIA filament stability and localization by phosphorylating key residues in its heavy chain. This phosphorylation impacts myosin IIA incorporation into the cytoskeleton, affecting cellular contractility and disease pathogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Myosin II-based contractility is crucial for cellular functions and its deregulation is implicated in diseases like cancer.
  • Tight spatial and temporal control of myosin II activity is essential for maintaining cellular homeostasis.
  • The mammalian alpha-kinase TRPM7 was previously shown to inhibit myosin II-based contractility, but the underlying molecular mechanism remained unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism by which TRPM7 regulates myosin II-based contractility.
  • To identify the specific sites and consequences of TRPM7-mediated phosphorylation on myosin IIA heavy chains.

Main Methods:

  • Phosphorylation site mapping of mouse and human myosin IIA heavy chains.
  • Site-directed mutagenesis of identified phosphorylation residues (Thr1800, Ser1803, Ser1808) to alanine and aspartic acid.
  • Analysis of myosin IIA incorporation into the actomyosin cytoskeleton and subcellular localization.

Main Results:

  • TRPM7 was demonstrated to directly phosphorylate the COOH-termini of mouse and human myosin IIA heavy chains at Thr1800, Ser1803, and Ser1808.
  • Mutating these residues to alanine increased myosin IIA incorporation into the cytoskeleton, while mutation to aspartic acid decreased it.
  • These mutations also affected the subcellular localization of myosin IIA, indicating a role in filament stability and organization.

Conclusions:

  • TRPM7 regulates myosin IIA filament stability and localization through phosphorylation of specific residues in the alpha-helical tail of the myosin IIA heavy chain.
  • This mechanism provides critical insights into the control of actomyosin dynamics and its implications in human diseases.

More Related Videos

Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications09:29

Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications

Published on: May 18, 2017

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag08:55

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

Related Concept Videos

Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Actin Treadmilling01:18

Actin Treadmilling

Actin filaments undergo polymerization and depolymerization from either end. The polymerization and depolymerization rates depend on the cytosolic concentration of free G-actins. The polymerization rate is generally higher at the plus or barbed end, while the depolymerization rate is higher at the minus or pointed end. At a steady state, critical concentration describes the concentration of free G-actin monomers at which the polymerization rate at the plus end is equal to that of the...
Disassembly of Intermediate Filaments01:35

Disassembly of Intermediate Filaments

Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...