Summary

Actin is a fundamental cytoskeletal protein that assembles into dynamic filaments to drive and support a vast array of cellular processes. Polymerisation of monomeric actin at one end of the filament and depolymerisation at the other establishes a treadmilling cycle that powers membrane protrusions, cell migration, intracellular transport and mechanical resilience. Actin networks are remodelled by specialised binding proteins that nucleate new filaments, stabilise or cap filament ends, sever existing polymers and cross-link filaments into higher-order architectures. These regulatory activities underpin the formation of lamellipodia and filopodia in motile cells, maintain the integrity of adherens junctions, orchestrate endocytic vesicle scission and facilitate the contractile apparatus of muscle. Dysregulation of actin dynamics contributes to developmental defects, cardiovascular disease, neurodegeneration and facilitates pathogen invasion. Understanding the molecular choreography of actin assembly and disassembly is thus critical for elucidating cell behaviour and for identifying novel therapeutic targets.

Research from Nature Portfolio

Recent studies have identified Tropomodulin 3 as a key effector of the insulin-activated kinase Akt2 pathway. Phosphorylation of Tropomodulin 3 promotes cortical actin remodelling, which is essential for the targeted insertion of glucose transporter vesicles into the plasma membrane. This work highlights how pointed-end capping proteins link signal transduction to membrane trafficking via direct control of filament dynamics. Complementing this, structural analyses have revealed how tropomodulin and its homologue leiomodin share a common fold yet perform distinct functions. Subtle adaptations in their actin-binding surfaces determine whether they cap the slow-growing end of filaments or instead nucleate new filament formation. This insight clarifies the mechanistic basis by which related proteins regulate actin architecture in muscle sarcomeres and other cellular contexts.

Actin Dynamics in Cellular Structures publication trend

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

Technical terms

Actin filament (F-actin): polymerised form of actin monomers that assembles into helical filaments.

Globular actin (G-actin): monomeric form of actin that serves as the building block for filament growth.

Polymerisation: process by which actin monomers add to the barbed or pointed ends of existing filaments, driving filament elongation.

Pointed-end capping: binding of specific proteins to the slow-growing end of an actin filament, preventing addition or loss of subunits.

Actin-binding protein (ABP): any of a large group of regulators that modulate filament nucleation, stability, cross-linking or severing.

References

  1. Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling. Nature Communications (2015).
  2. How Leiomodin and Tropomodulin use a common fold for different actin assembly functions. Nature Communications (2015).
  3. Role of Actin-Binding Proteins in Skeletal Myogenesis. Cells (2023).
  4. Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics. Biomolecules (2023).
  5. Novel secreted STPKLRR from Vibrio splendidus AJ01 promotes pathogen internalization via mediating tropomodulin phosphorylation dependent cytoskeleton rearrangement. PLOS Pathogens (2023).
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