Intermediate filaments: from cell architecture to nanomechanics

Key Points Intermediate filaments (IFs) are assembled from fibrous proteins that exhibit a central α-helical rod domain with a conserved substructure. This rod domain facilitates the formation of dimeric coiled-coil complexes. In metazoan cells, IF proteins constitute two distinct filament systems: one in the nucleus and one in the cytoplasm. In both cases, the major function of these filaments is thought to be the buffering of mechanical stress. In conjunction with associated proteins, IFs generate networks that serve to generate and support the shape of cells. Recent nanomechanical experiments have demonstrated that IFs are characterized by a high propensity to withstand both tensile and bending stress. In line with this, disease mutations in human IF proteins indicate that the nanomechanical properties of cell-type-specific IFs are central to the pathogenesis of these diseases. Apart from structural functions, the analysis of complex diseases, such as cardiomyopathies, has revealed that IFs also have a significant role in cell-type-specific physiological functions and even contribute to the regulation of gene-expression programmes. Intermediate filaments (IFs) are thought to function as absorbers of mechanical stress and form cytoskeletal networks that serve to support cell shape. The analysis of disease-causing mutations in IF proteins has revealed that IFs also have important roles in cell-type-specific physiological functions. Intermediate filaments (IFs) constitute a major structural element of animal cells. They build two distinct systems, one in the nucleus and one in the cytoplasm. In both cases, their major function is assumed to be that of a mechanical stress absorber and an integrating device for the entire cytoskeleton. In line with this, recent disease mutations in human IF proteins indicate that the nanomechanical properties of cell-type-specific IFs are central to the pathogenesis of diseases as diverse as muscular dystrophy and premature ageing. However, the analysis of these various diseases suggests that IFs also have an important role in cell-type-specific physiological functions.