Intermediate filaments: primary determinants of cell architecture and plasticity
Harald Herrmann, Sergei V. Strelkov, Peter Burkhard, Ueli Aebi
Harald Herrmann, Sergei V. Strelkov, Peter Burkhard, Ueli Aebi
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Intermediate filaments: primary determinants of cell architecture and plasticity

Abstract

Intermediate filaments (IFs) are major constituents of the cytoskeleton and nuclear boundary in animal cells. They are of prime importance for the functional organization of structural elements. Depending on the cell type, morphologically similar but biochemically distinct proteins form highly viscoelastic filament networks with multiple nanomechanical functions. Besides their primary role in cell plasticity and their established function as cellular stress absorbers, recently discovered gene defects have elucidated that structural alterations of IFs can affect their involvement both in signaling and in controlling gene regulatory networks. Here, we highlight the basic structural and functional properties of IFs and derive a concept of how mutations may affect cellular architecture and thereby tissue construction and physiology.

Authors

Harald Herrmann, Sergei V. Strelkov, Peter Burkhard, Ueli Aebi

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Figure 6

Molecular characterization of the desmin mutants A360P and R406W.

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Molecular characterization of the desmin mutants A360P and R406W. (A) Ma...
(A) Mass measurement of assembled wild-type desmin (WT) filaments in comparison with filaments formed by the mutant A360P. Nonstained, lightly fixed filaments were analyzed by scanning transmission electron microscopy and visualized in a dark field mode (first and third panels from the left). The rectangles indicate the areas used for the quantification of mass. One side of the square is 60-nm long. The molecular mass of individual filaments was determined along the various individual filaments and plotted as kDa/nm into a histogram (second and fourth panels from the left). The abscissa shows mass in kDa/nm; the ordinate shows the number of segments analyzed. (B) Filament assembly of wild-type desmin in comparison to that of the mutant R406W, as depicted by electron microscopy of negatively stained samples obtained at 10 seconds and 1 hour. Scale bar: 100 nm. (C) C-terminal region of the wild-type desmin dimer (left panel) compared with the R406W mutant (right panel). The mutated amino acid is shown in magenta. The change of arginine (R406) to tryptophan (W406) destroys the salt bridge formed with E401. The atomic model is based on the known crystal structure of the corresponding vimentin fragment. The figure is a composite of figures adapted with permission from Journal of molecular biology and Journal of structural biology (110, 131).