Cytoskeletal Dynamics in Smooth Muscle Function

The contractile function of smooth muscle relies on the dynamic interplay of three principal cytoskeletal networks: actin filaments, intermediate filaments and microtubules. Actin polymerisation and depolymerisation at the cell cortex generate forces transmitted through focal adhesions to the extracellular matrix, driving tension and cell shape changes. Intermediate filaments such as vimentin and nestin provide structural resilience and coordinate signal transduction during contraction, migration and proliferation. Microtubules establish polarity and serve as tracks for intracellular trafficking of signalling molecules and organelles, supporting front–rear asymmetry in migrating cells and ensuring efficient mitotic spindle assembly. Kinases including Abelson tyrosine kinase and polo-like kinase 1 orchestrate cytoskeletal remodelling through site-specific phosphorylation of adaptor proteins and filament subunits. This spatial-temporal regulation enables smooth muscle to adapt to physiological demands, underpinning processes from airway tone regulation to vascular homeostasis. Dysregulated cytoskeletal dynamics contribute to pathologies such as asthma, hypertension and vascular remodelling. Recent advances have illuminated the molecular crosstalk among cytoskeletal systems, revealing novel nodes for therapeutic intervention and offering a unified framework for understanding smooth muscle function across organ systems.

Research from Nature Portfolio

Investigations have revealed that microRNA-509 targets the serine/threonine kinase polo-like kinase 1 to modulate mitogen-activated pathways in airway smooth muscle. By downregulating polo-like kinase 1, microRNA-509 suppresses MEK/ERK signalling, attenuates vimentin filament reorganisation and impairs focal adhesion assembly, thereby reducing cell migration. Complementary work has identified a critical role for polo-like kinase 1 in phosphorylating paxillin at Ser-272, a modification required for centrosome maturation and efficient spindle assembly. In models of allergic asthma, this phosphorylation event drives airway smooth muscle layer thickening and hyperplasia. Further studies have defined Abelson interactor 1 (Abi1) as a scaffold at the leading edge of migrating smooth muscle cells, where it recruits profilin-1 and neuronal Wiskott–Aldrich syndrome protein to coordinate actin polymerisation. Knockdown of Abi1 disrupts lamellipodial protrusion and reduces cell motility, underscoring the importance of Abi1 in cytoskeletal organisation during migration.

Research from all publishers

New findings highlight nestin as a central regulator of cytoskeletal signalling in airway smooth muscle. Loss of nestin diminishes the recruitment of cortactin and profilin-1 to the plasma membrane, reduces polo-like kinase 1 activation and vimentin phosphorylation, and impairs actin polymerisation and contractile responses. A parallel study demonstrates that nestin controls smooth muscle cell migration by organising the vimentin network and modulating focal adhesion size; nestin knockdown leads to reduced polo-like kinase 1 phosphorylation, altered vimentin–paxillin interactions and smaller adhesion complexes, culminating in attenuated cell motility.

Cytoskeletal Dynamics in Smooth Muscle Function publication trend

The graph below shows the total number of articles in cytoskeletal dynamics in smooth muscle function across all publications each year (not limited to Nature Index journals).

Technical terms

Actin polymerisation: The assembly of globular actin monomers into filamentous structures that generate contractile force.

Intermediate filaments: Cable-like protein assemblies (e.g. vimentin, nestin) providing mechanical support and organising signal transduction.

Microtubules: Polarised tubulin polymers that form tracks for intracellular transport and contribute to cell polarity and division.

Focal adhesions: Multiprotein complexes linking the actin cytoskeleton to the extracellular matrix, mediating force transmission and signalling.

Phosphorylation: The enzymatic addition of a phosphate group to a protein, often regulating its activity, localisation or interactions.

References

1. The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration. Respiratory Research (2017).
2. Role and regulation of Abelson tyrosine kinase in Crk-associated substrate/profilin-1 interaction and airway smooth muscle contraction. Respiratory Research (2018).
3. MicroRNA miR-509 Regulates ERK1/2, the Vimentin Network, and Focal Adhesions by Targeting Plk1. Scientific Reports (2018).
4. Plk1 Mediates Paxillin Phosphorylation (Ser-272), Centrosome Maturation, and Airway Smooth Muscle Layer Thickening in Allergic Asthma. Scientific Reports (2019).
5. Distinctive roles of Abi1 in regulating actin-associated proteins during human smooth muscle cell migration. Scientific Reports (2020).
6. The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling. Respiratory Research (2023).
7. Nestin Modulates Airway Smooth Muscle Cell Migration by Affecting Spatial Rearrangement of Vimentin Network and Focal Adhesion Assembly. Cells (2022).