Regulation of Actin Dynamics in Cellular Processes

Actin dynamics lie at the heart of numerous cellular functions, from the generation of force during motility to the organisation of intracellular architecture and the transduction of biochemical signals. The rapid polymerisation and disassembly of actin filaments enable cells to adopt diverse shapes, migrate in response to external cues and orchestrate division and vesicular trafficking. A finely tuned network of actin-binding proteins—including nucleators, severing factors, capping proteins and monomer-binding partners—collaborates with Rho family GTPase signalling to regulate filament assembly, branching and turnover. Feedback mechanisms, such as mechanochemical sensing and calcium-mediated resets of the cortical actin network, ensure that filament dynamics adapt swiftly to changing physiological demands. Dysregulation of these pathways underlies a wide spectrum of human disorders, from kidney degeneration and peripheral neuropathies to impaired immune responses and cancer cell invasion. Advances in imaging, structural analysis and small-molecule modulation have begun to unveil the molecular logic of actin regulation and its potential as a therapeutic target.

Research from Nature Portfolio

Structural and cellular analyses of disease-associated INF2 variants have revealed how subtle disruptions in an actin assembly factor can precipitate organ-specific pathology. Variants linked to focal segmental glomerulosclerosis (FSGS) and combined Charcot–Marie–Tooth (CMT/FSGS) disease differ in their impact on actin stress fibres, microtubule arrays and mitochondrial distribution, correlating with the severity of cytoskeletal disorganisation. These findings underscore the importance of precise intramolecular controls that maintain INF2 in an inactive state until activated by physiological signals. In parallel, work on the small-molecule SMIFH2 has clarified the dual consequences of pharmacological formin inhibition: acute perturbation of filamentous actin dynamics is accompanied by oscillatory remodelling of microtubules and Golgi architecture, as well as downregulation of p53. This study has emphasised the need for careful titration and exposure time when employing formin inhibitors in cellular assays to avoid off-target effects and cytotoxicity.

Regulation of Actin Dynamics in Cellular Processes publication trend

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

Technical terms

Actin polymerisation: The process by which globular actin monomers assemble into filamentous structures that provide mechanical support and drive cellular movements.

Formins: A family of actin nucleation factors that promote the elongation of unbranched actin filaments through their formin homology domains.

G-actin: Monomeric form of actin, which can be sequestered or released to regulate filament formation.

F-actin: Polymerised, filamentous form of actin that constitutes the cytoskeletal backbone.

Endoplasmic reticulum (ER): A network of membranous tubules involved in protein synthesis, lipid metabolism and calcium storage, whose morphology is influenced by actin–membrane interactions.

Hetero-oligomer: A complex of two or more distinct protein molecules that interact to perform a cooperative function, such as mDia1–mDia2 filament regulation.

FSGS (focal segmental glomerulosclerosis): A kidney disorder characterised by scarring of glomeruli and associated with podocyte actin cytoskeleton defects.

CMT (Charcot–Marie–Tooth disease): A hereditary neuropathy involving progressive loss of peripheral nerve function linked to cytoskeletal dysregulation in Schwann cells and neurons.

References

1. Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy. Scientific Reports (2023).
2. SMIFH2 has effects on Formins and p53 that perturb the cell cytoskeleton. Scientific Reports (2015).
3. Calcium-mediated actin reset (CaAR) mediates acute cell adaptations. eLife (2016).
4. Altered Endoplasmic Reticulum Integrity and Organelle Interactions in Living Cells Expressing INF2 Variants. International Journal of Molecular Sciences (2024).
5. mDia formins form hetero-oligomers and cooperatively maintain murine hematopoiesis. PLOS Genetics (2023).
6. Actin Monomers Activate Inverted Formin 2 by Competing with Its Autoinhibitory Interaction*. Journal of Biological Chemistry (2013).