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INTERMEDIATE FILAMENTS FROM CELL ARCHITECTURE TO NANOMECHANICS PDF

Intermediate filaments: from cell architecture to nanomechanics. Type: Article; Author(s): Harald Herrmann, Harald Bär, Laurent Kreplak, Sergei V. Strelkov, Ueli . 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. Herrmann, H. and Baer, H. and Kreplak, L. and Strelkov, S. and Aebi, U.. () Intermediate Filaments: from Cell Architecture to.

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Intermediate filaments: primary determinants of cell architecture and plasticity

In contrast, the nestin head domain is unusually short, with only six amino acids. The initial crystallization studies were followed by the determination of the atomic structure of coil 1A and the second half of coil 2, then called coil 2B, for both vimentin and lamin A 43 Adapted with permission from Journal of biological chemistry Interestingly, when monitoring the breaking process, a phase where the filament becomes more viscoelastic in response to the applied strain was clearly visualized Figure 7 C.

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. Some mutant desmins form short IFs that eventually convert into sheet-like assemblies, whereas others convert into small ball-like aggregates Weitz Current opinion in cell biology Interestingly, mutations located very close to one another within the molecule can give rise to entirely different in vitro assembly phenotypes.

These types of interactions may represent major molecular contacts mediating the longitudinal annealing of ULFs and short filaments. The rectangles indicate the areas used for the quantification of mass. ShipmanPaul G. Hence, lamins, vimentin-like IF proteins, and keratins will not coassemble into mixed IFs; rather, they completely segregate into distinct structures, even within the same cell In the middle of coil 2B, a discontinuity in the heptad repeat pattern, a so-called stutteris consistently found in all IF proteins.

When transfected into fibroblasts, the two groups of desmin mutants described above those that form extended filaments and those that cannot give rise to two distinct cell phenotypes. Thirteen genes encode mesenchymal, muscle, lens-specific, and neuronal IF proteins, and three genes encode the four nuclear lamins This conserved assembly behavior indicates that structural and functional aspects coevolved early on, even before vertebrate development started.

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Desmin mutations affect IF assembly. Their absence may correlate with the fact that the body plan of plants and fungi depends on mechanical support provided by external cell walls. C C-terminal region of the wild-type desmin dimer left panel compared with the RW mutant right panel. The functional meaning for this similarity is at present not clear.

The mutated amino acid is shown in magenta.

Hence, these mutations in K5 and K14 interfere with the proper generation of a functional cytoskeleton and, as a consequence, with the stress-absorbing functions of IFs. From This Paper Figures and tables from this paper. Hence, IF proteins are found in simple animals, such as the sweet water sponge Hydra and the nematode Caenorhabditis. Moreover, these cells display reduced mechanical stability, motility, and directional migration.

Intermediate filaments: from cell architecture to nanomechanics | University College London

In addition, an increasing number of alternative splice forms of individual IF proteins have been discovered recently 5. A Schematic representation of the structural organization of an IF molecule.

The relation of mutations to disease severity is surely connected in part to such functions. Although, the respective pathomechanisms have remained elusive, several plausible suggestions bearing on their central role as archiitecture of cellular architecture have been made.

L1, L12, and L2 are linker segments. Hence, it is their ability to longitudinally anneal that is affected Figure 6 B.

The nuclear IF system in interphase cells constitutes a meshwork-like lamina of partially heterogeneous and independently organized filaments made of lamin A, lamin C, lamin B 1and lamin B 2 In contrast to actin and tubulin, which are globular proteins, IF proteins are fibrous.

Furthermore, the extended filaments observed after 1 hour of in vitro assembly exhibit alterations in their networking ability, indicating a defect in their higher order organization Nevertheless, in the full-length protein, coil 1A is not isolated but embedded in a distinct structural context, and larger fragments containing the head domain in addition to coil 1A behave, under certain in vitro conditions, like a dimeric coiled coil Skip to search form Skip to main content.

B Filament assembly of wild-type desmin in comparison to that of the mutant RW, as depicted by electron microscopy of negatively stained samples obtained at 10 seconds and 1 hour. They are of prime importance for the functional organization of structural elements. As expected, with the study of a larger number of desmin disease-associated mutants, a more complex picture emerged: Future studies in transgenic animals will surely further our understanding of the differences found in the mechanical properties of individual mutant desmins In phase 1, eight tetrameric subunits made from two antiparallel, half-staggered coiled-coil dimers associate laterally to form ULFs after initiation of assembly.

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Moreover, as observed in patients, all reported myopathic desmin mutations eventually lead to the generation of aggregates that contain mutant desmin, wild-type desmin, and many more proteins of the myocyte cytoskeleton; the molecular mechanism by which the organization of the extra-sarcomeric cytoskeleton is affected by the aggregates is still elusive. View this article via: Although in silico structural prediction served well for some time to describe the structure of IF proteins, our recent crystallographic studies our unpublished observations indicate that certain adjustments to the earlier picture of the second half of the rod are needed.

Intermediate Filaments: from Cell Architecture to Nanomechanics – edoc

First published July 1, – Version history. Analysis of the effects of the mutation, which led to a deletion of seven amino acids in coil 1B, demonstrated that it compromised desmin IF assembly both in vitro and in transfected cells. As a consequence, the skin of people born with defective K14 is highly fragile The molecular basis for the special viscoelastic behavior of IFs has been worked out using rheological methods In the case of the myocyte cytoskeleton, there is further nanomechanicz, as it contains IF proteins, such as synemin and syncoilin, that are unable to self-assemble into filaments but need desmin as a scaffold for coassembly, probably by forming heterodimers or higher order complexes with desmin.

Considering such conservation of amino acid sequence among diverse species, it comes as no surprise that mutations in these motifs interfere drastically with the function of IF proteins. C Transfection of mouse nxnomechanics fibroblasts derived from vimentin-knockout mice with the vimentin mutant YL, followed by indirect immunofluorescence microscopy with antibodies specific for human vimentin, revealing dot-like structures exclusively.

D Merged image of A — C.