Formins in Actin Cytoskeleton Dynamics

Formins are a conserved family of actin-binding proteins that orchestrate the formation and elongation of unbranched actin filaments, thereby shaping the architecture and mechanical properties of the cytoskeleton. Central to their function are two conserved regions: the Formin Homology 1 (FH1) domain, which recruits profilin–actin complexes, and the Formin Homology 2 (FH2) domain, which processively caps and nucleates filament barbed ends. Through dynamic regulation of filament growth and bundling, formins underpin processes as diverse as lamellipodial and filopodial protrusion, stress fibre assembly, cytokinetic ring formation and intracellular vesicle trafficking. In addition to biochemical control, formins respond to mechanical cues—sensing tensile forces and torque—to modulate polymerisation rates in vivo. This mechanochemical versatility links formins to cell migration, division, immune cell function and pathological states such as tumour invasion.

Research from Nature Portfolio

Recent studies have uncovered how mechanical inputs regulate formin activity at the single-molecule level and in cellular structures. One investigation demonstrated that application of piconewton forces to individual actin filaments accelerates mDia1-mediated polymerisation by biasing the FH2 domain toward an open conformation, while also revealing that torque sensitivity is integral to force-dependent velocity changes. A complementary study showed that formin Cdc12 in fission yeast senses myosin-generated pulling forces during cytokinesis; mechanical inhibition of Cdc12’s FH1 domain modulates ring assembly dynamics and ensures robust contractile ring formation. Together, these findings cast formins as bona fide mechanosensors that integrate force feedback to regulate actin architecture during cell division and mechanical adaptation.

Formins in Actin Cytoskeleton Dynamics publication trend

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

Technical terms

Formin: A dimeric actin-polymerising protein characterised by FH1 and FH2 domains that nucleates and processively elongates unbranched actin filaments.

FH1 domain: A proline-rich region that binds profilin–actin complexes, delivering actin monomers to the FH2-bound barbed end.

FH2 domain: A helical bundle that dimerises to cap the filament barbed end and mediate processive elongation.

Barbed end: The rapidly growing end of an actin filament where subunit addition predominantly occurs.

Profilin: A small actin-binding protein that sequesters actin monomers and interacts with FH1 domains to regulate filament assembly.

Mechanosensing: The ability of a protein or complex to detect and respond to mechanical forces or deformations, altering its activity accordingly.

References

1. Vesicle‐Associated Actin Assembly by Formins Promotes TGFβ‐Induced ANGPTL4 Trafficking, Secretion and Cell Invasion. Advanced Science (2023).
2. Identification of an FMNL2 Interactome by Quantitative Mass Spectrometry. International Journal of Molecular Sciences (2024).
3. Profilin and formin constitute a pacemaker system for robust actin filament growth. eLife (2019).
4. mDia1 senses both force and torque during F-actin filament polymerization. Nature Communications (2017).
5. Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly. Nature Communications (2017).