Redox Regulation of Actin Cytoskeleton Dynamics

The dynamic assembly and disassembly of actin filaments underpin essential cellular behaviours including migration, morphogenesis and division. Emerging evidence reveals that reversible oxidation–reduction (redox) events modulate actin’s structural states and its interactions with regulatory proteins. Specific redox enzymes, notably the MICAL family of flavoprotein monooxygenases, directly oxidise filamentous actin (F-actin) and promote rapid disassembly. Meanwhile, cellular sources of reactive oxygen species can induce actin glutathionylation, altering filament stability and network organisation. Together, these redox controls integrate extracellular cues and intracellular signalling pathways to fine-tune cytoskeletal architecture, with implications for wound healing, immune responses and development.

Research from Nature Portfolio

Structural studies have elucidated the autoinhibition and activation mechanisms of MICAL1. Cryo-EM and biochemical analyses reveal that intramolecular contacts between the catalytic monooxygenase domain and a C-terminal coiled-coil block F-actin binding. Conformational changes in the coiled-coil and binding of accessory domains unleash the enzyme’s redox activity, providing a template for understanding MICAL regulation in diverse cellular contexts.

Single-filament imaging has characterised the rapid disassembly of oxidised actin. Investigations show that MICAL-oxidation of methionine residues 44 and 47 triggers structural rearrangements in the actin D-loop, creating a novel intermolecular contact that destabilises filaments. Mutagenesis studies confirm that this oxidation-induced contact accelerates F-actin depolymerisation, even in the presence of stabilising inorganic phosphate.

Seminal work has defined the MICAL protein family as conserved F-actin dismantling oxidoreductases. Biochemical assays demonstrate that each MICAL isoform uses NADPH-dependent redox chemistry to selectively oxidise actin, directly dismantling filaments and limiting polymerisation. Genetic experiments further illustrate how MICALs reshape cell morphology in vivo, with specific reductases counteracting their action to restore cytoskeletal integrity.

Redox Regulation of Actin Cytoskeleton Dynamics publication trend

The graph below shows the total number of articles in redox regulation of actin cytoskeleton dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Actin cytoskeleton: Network of filamentous proteins providing structural support and enabling cellular movement.

F-actin: Polymerised form of actin subunits assembled into filaments.

G-actin: Monomeric globular actin that assembles into filaments.

Redox reaction: Chemical process involving transfer of electrons, affecting protein structure and function.

MICAL: Flavoprotein monooxygenase that oxidatively modifies actin to regulate filament dynamics.

Glutathionylation: Reversible attachment of glutathione to cysteine residues, modulating protein activity.

References

1. Structural basis of MICAL autoinhibition. Nature Communications (2024).
2. Catastrophic disassembly of actin filaments via Mical-mediated oxidation. Nature Communications (2017).
3. The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans. Scientific Reports (2018).
4. Reorganization of the actin cytoskeleton during the formation of neutrophil extracellular traps (NETs). European Journal of Cell Biology (2024).
5. MICAL-mediated oxidation of actin and its effects on cytoskeletal and cellular dynamics. Frontiers in Cell and Developmental Biology (2023).
6. Redox Regulation of β-Actin during Integrin-mediated Cell Adhesion*. Journal of Biological Chemistry (2006).