Vimentin Diversity in Health and Disease

Abstract

Vimentin is a protein that has been linked to a large variety of pathophysiological conditions, including cataracts, Crohn's disease, rheumatoid arthritis, HIV and cancer. Vimentin has also been shown to regulate a wide spectrum of basic cellular functions. In cells, vimentin assembles into a network of filaments that spans the cytoplasm. It can also be found in smaller, non-filamentous forms that can localise both within cells and within the extracellular microenvironment. The vimentin structure can be altered by subunit exchange, cleavage into different sizes, re-annealing, post-translational modifications and interacting proteins. Together with the observation that different domains of vimentin might have evolved under different selection pressures that defined distinct biological functions for different parts of the protein, the many diverse variants of vimentin might be the cause of its functional diversity. A number of review articles have focussed on the biology and medical aspects of intermediate filament proteins without particular commitment to vimentin, and other reviews have focussed on intermediate filaments in an in vitro context. In contrast, the present review focusses almost exclusively on vimentin, and covers both ex vivo and in vivo data from tissue culture and from living organisms, including a summary of the many phenotypes of vimentin knockout animals. Our aim is to provide a comprehensive overview of the current understanding of the many diverse aspects of vimentin, from biochemical, mechanical, cellular, systems biology and medical perspectives.

Keywords: biomechanics; cancer and metastasis; cell mechanical stiffness or elasticity; cellular contractility; cell‒extracellular matrix adhesions; clinical biomarkers; drug target; epithelial‒mesenchymal transition; extracellular vimentin; intermediate filaments; tissue regeneration; vimentin.

Figure 1

(A) The amino acid sequence of vimentin rod domain, with the amino acid position in the sequence indicated above the one-letter code. Heptad (not coloured) and hendecad (violet) motifs are indicated. Residues predicted to be buried in the hydrophobic core are highlighted in yellow. The coil 1A, linker 1, coil 1B, coil 2 structures are indicated with pink, red, violet, and blue, respectively. (B) Schematic structure of a vimentin dimer (top) and tetramer (bottom) showing the antiparallel association of two coiled coil dimers, with the structures indicated with colours as in A. Each dimer is formed by a pair of parallel chains. The figure is adapted from Figure 4 in Chernyatina, PNAS 2015 [36], and based on data by Chernyatina, PNAS 2012 [37].

Figure 2

Example of tissue groups in which vimentin protein has been identified in low, medium or high levels. Gender-neutral and gender-specific tissue groups are indicated by blue or white squares, respectively.

Figure 3

Examples of how the vimentin protein control cells, on a molecular (top), cellular (middle) and extracellular (bottom) level.

Figure 4

Diseases linked to defective functions of the vimentin protein. Neoplasms are shown in blue boxes, other pathologies in grey boxes.