Role of Intermediate Filaments in Cell Locomotion


Cell locomotion is essential for diverse pathophysiological processes, including embryogenesis, immune responses, wound healing and cancer metastasis. Intermediate filaments (IFs) are resilient cytoskeleton components that provide structural support and mechanical protection. Accumulating evidence suggests that IFs are dynamic structures that function as a scaffold for signalling networks, which regulate cell locomotion, shape change and mechanical responses. The dynamics of IFs are regulated by posttranslational modifications, crosstalk with other cytoskeletons and association with cell adhesion complexes. IFs differentially regulate cell locomotion, depending on the particular IF protein, the cell type, the cellular context and the mode of cell migration. In general, vimentin filaments promote and keratin filaments inhibit cell locomotion. These cytoplasmic IFs regulate cell locomotion by modulating the localisation and activity of signalling molecules and influencing the stability of cell–cell and cell–substrate adhesion complexes. Nuclear lamin‐A represses cell locomotion by stiffening the nucleus.

Key Concepts

  • Intermediate filaments (IFs) constitute the resilient cytoskeleton that provides structural support and protects cells from external forces.
  • IFs function as a dynamic scaffold for signalling networks that regulate locomotion, shape change and mechanical responses.
  • Cytoplasmic IFs are linked to desmosomes and hemidesmosomes at cell adhesion sites and linker of nucleoskeleton and cytoskeleton (LINC) complexes on the nuclear membrane.
  • The reorganisation and dynamics of IFs are regulated by posttranslational modifications, crosstalk with other cytoskeletons and association with cell adhesion complexes.
  • IFs differentially regulate cell locomotion, depending on the particular IF protein, the cell type, the cellular context and the mode of cell migration.
  • Vimentin IFs generally promote cell locomotion by destabilising desmosomes, promoting focal adhesion maturation and affecting the activity of signalling molecules.
  • Keratin IFs generally repress cell locomotion by stabilising desmosomes and hemidesmosomes and affecting the localisation and activity of signalling molecules.
  • Nuclear lamin‐A represses cell locomotion by stiffening the nucleus.
  • Keratin IFs and Rho signalling are mutually regulated, providing a feedback mechanism during mechanical responses.

Keywords: intermediate filament; cytoskeleton; posttranslational modification; cell migration; hemidesmosome; desmosome; linker of nucleoskeleton and cytoskeleton (LINC) complex; focal adhesion; mechanosensing; Rho family

Figure 1. (a) Structure of an intermediate filament (IF) protein. An monomer IF has a common domain structure consisting of an N‐terminal head domain, a central rod domain and a C‐terminal tail domain. The rod domain comprises α‐helical segments (1A, 1B, 2A and 2B) and nonhelical short spacer sequences. The amino acid sequences of the rod domain are highly conserved among all IF proteins, but the head and tail domains differ considerably in size and sequence. (b) Assembly of IFs. Two monomers form a parallel coiled‐coil dimer; two dimers associate to form an antiparallel tetramer, which is the basic assembly unit; eight tetramers laterally assemble to form a unit‐length filament (ULF); ULFs anneal longitudinally to form nonpolar filaments, which then undergo radial compaction to form mature cytoplasmic IFs of ∼10‐nm diameter. Nuclear lamins are composed of tetrameric filaments of ∼3.5‐nm diameter.
Figure 2. Intermediate filament (IF)‐coupled adhesion complexes. (a) Location of IF‐coupled adhesion complexes in cells. (b) Schematic structure of desmosome. Desmosomes are formed at cell–cell adhesions of epithelia and cardiac muscle cells and anchor IFs to form a bridge between neighbouring cells. (c) Schematic structure of hemidesmosome. Hemidesmosomes mediate cell–extracellular matrix (ECM) adhesion of epithelial cells and anchor IFs to integrins. (d) Schematic structure of the linker of nucleoskeleton and cytoskeleton (LINC) complex. The LINC complex is located on the nuclear envelope and indirectly connects cytoplasmic IFs to nuclear lamins. BP230, bullous pemphigoid 230; CD151, clusters of differentiation 151; Nesprin‐3, nuclear envelope spectrin repeat protein 3 and Sun, Sad1 and UNC‐84.
Figure 3. Key effects of intermediate filaments (IFs) and IF‐coupled adhesion complexes on cell locomotion. (a) The cell locomotion cycle. (1) The lamellipodial membrane protrusion is extended towards the direction of cell movement. (2) The lamellipodium attachment to the substrate initiates the formation of focal adhesions and hemidesmosomes. (3) The focal adhesions anchor stress fibres, which generate contractile forces and promote traction of the cell body. (4) The tail detaches from the substrate and retracts to the cell body. (b) Typical effects of cytoplasmic and nuclear IFs on cell locomotion. Blue lines represent cytoplasmic IFs; orange lines and networks represent actin filaments and the dark blue dotted line represents nuclear lamins. Commentaries in red and dark blue letters indicate the positive and negative impacts on cell movement, respectively.


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Fujiwara, Sachiko, and Mizuno, Kensaku(Jul 2017) Role of Intermediate Filaments in Cell Locomotion. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026365]