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5.1
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Cells
Special Issues
Beyond Cell Mechanics: Novel Functions of Intermediate Filaments
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Beyond Cell Mechanics: Novel Functions of Intermediate Filaments

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (20 February 2016) | Viewed by 85713

Special Issue Editor

Dr. Rudolf E. Leube

E-Mail Website
Guest Editor
Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany
Interests: epithelia; cytoskeleton; junctions; mechanobiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The compositional diversity of cytoplasmic intermediate filaments supports cell type-specific function in metazoan cells. Besides providing a highly adaptable mechanical scaffold that is anchored to neighboring cells and the extracellular matrix, intermediate filaments support many cellular processes. These include signaling, gene regulation, vesicle trafficking, mitochondrial function, and cell fate determination. Intermediate filaments are also involved in pathologies, such as inflammation, organ-specific diseases, and cancer. It is a common belief that the abundance of intermediate filaments makes them an ideal buffer system for protecting cells against any kind of insult, be it physical, chemical or microbial.

Challenging questions that we currently face include:

  • How do intermediate filament mechanics affect cell function?
  • How can we measure and examine the consequences of minor changes in low affinity interactions of intermediate filaments in the context of long-term tissue function?
  • How do cytoplasmic intermediate filaments integrate tissue function?
  • What are the molecular mechanisms that determine isotype-specific intermediate filament functions?

This current volume aims to present novel ideas and hypotheses as to intermediate filament function in specific cellular and tissue contexts.

Prof. Dr. Rudolf E. Leube
Guest Editor

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Keywords

  • intermediate filaments
  • mechanics
  • migration
  • signaling
  • transcription
  • vesicle trafficking
  • mitochondrial function
  • stress response
  • inflammation
  • cancer
  • disease

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Published Papers (8 papers)

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Research

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3271 KiB  
Article
Vimentin Levels and Serine 71 Phosphorylation in the Control of Cell-Matrix Adhesions, Migration Speed, and Shape of Transformed Human Fibroblasts
by Emmanuel Terriac, Giovanna Coceano, Zahra Mavajian, Tijmen A. G. Hageman, Andreas F. Christ, Ilaria Testa, Franziska Lautenschläger and Annica K. B. Gad
Cells 2017, 6(1), 2; https://doi.org/10.3390/cells6010002 - 22 Jan 2017
Cited by 41 | Viewed by 8235
Abstract
Metastasizing tumor cells show increased expression of the intermediate filament (IF) protein vimentin, which has been used to diagnose invasive tumors for decades. Recent observations indicate that vimentin is not only a passive marker for carcinoma, but may also induce tumor cell invasion. [...] Read more.
Metastasizing tumor cells show increased expression of the intermediate filament (IF) protein vimentin, which has been used to diagnose invasive tumors for decades. Recent observations indicate that vimentin is not only a passive marker for carcinoma, but may also induce tumor cell invasion. To clarify how vimentin IFs control cell adhesions and migration, we analyzed the nanoscale (30–50 nm) spatial organization of vimentin IFs and cell-matrix adhesions in metastatic fibroblast cells, using three-color stimulated emission depletion (STED) microscopy. We also studied whether wild-type and phospho-deficient or -mimicking mutants of vimentin changed the size and lifetime of focal adhesions (FAs), cell shape, and cell migration, using live-cell total internal reflection imaging and confocal microscopy. We observed that vimentin exists in fragments of different lengths. Short fragments were mostly the size of a unit-length filament and were mainly localized close to small cell-matrix adhesions. Long vimentin filaments were found in the proximity of large FAs. Vimentin expression in these cells caused a reduction in FAs size and an elongated cell shape, but did not affect FA lifetime, or the speed or directionality of cell migration. Expression of a phospho-mimicking mutant (S71D) of vimentin increased the speed of cell migration. Taken together, our results suggest that in highly migratory, transformed mesenchymal cells, vimentin levels control the cell shape and FA size, but not cell migration, which instead is linked to the phosphorylation status of S71 vimentin. These observations are consistent with the possibility that not only levels, but also the assembly status of vimentin control cell migration. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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9104 KiB  
Article
Keratins Are Altered in Intestinal Disease-Related Stress Responses
by Terhi O. Helenius, Cecilia A. Antman, Muhammad Nadeem Asghar, Joel H. Nyström and Diana M. Toivola
Cells 2016, 5(3), 35; https://doi.org/10.3390/cells5030035 - 10 Sep 2016
Cited by 19 | Viewed by 6979
Abstract
Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the [...] Read more.
Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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Review

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9294 KiB  
Review
Intermediate Filaments and Polarization in the Intestinal Epithelium
by Richard A. Coch and Rudolf E. Leube
Cells 2016, 5(3), 32; https://doi.org/10.3390/cells5030032 - 15 Jul 2016
Cited by 36 | Viewed by 11763
Abstract
The cytoplasmic intermediate filament cytoskeleton provides a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. This is particularly apparent in the intestinal epithelium, in which the intermediate filament network is localized below the apical terminal web region and is anchored to the apical [...] Read more.
The cytoplasmic intermediate filament cytoskeleton provides a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. This is particularly apparent in the intestinal epithelium, in which the intermediate filament network is localized below the apical terminal web region and is anchored to the apical junction complex. This arrangement is conserved from the nematode Caenorhabditis elegans to humans. The review summarizes compositional, morphological and functional features of the polarized intermediate filament cytoskeleton in intestinal cells of nematodes and mammals. We emphasize the cross talk of intermediate filaments with the actin- and tubulin-based cytoskeleton. Possible links of the intermediate filament system to the distribution of apical membrane proteins and the cell polarity complex are highlighted. Finally, we discuss how these properties relate to the establishment and maintenance of polarity in the intestine. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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993 KiB  
Review
Intermediate Filaments as Organizers of Cellular Space: How They Affect Mitochondrial Structure and Function
by Nicole Schwarz and Rudolf E. Leube
Cells 2016, 5(3), 30; https://doi.org/10.3390/cells5030030 - 5 Jul 2016
Cited by 57 | Viewed by 11326
Abstract
Intermediate filaments together with actin filaments and microtubules form the cytoskeleton, which is a complex and highly dynamic 3D network. Intermediate filaments are the major mechanical stress protectors but also affect cell growth, differentiation, signal transduction, and migration. Using intermediate filament-mitochondrial crosstalk as [...] Read more.
Intermediate filaments together with actin filaments and microtubules form the cytoskeleton, which is a complex and highly dynamic 3D network. Intermediate filaments are the major mechanical stress protectors but also affect cell growth, differentiation, signal transduction, and migration. Using intermediate filament-mitochondrial crosstalk as a prominent example, this review emphasizes the importance of intermediate filaments as crucial organizers of cytoplasmic space to support these functions. We summarize observations in different mammalian cell types which demonstrate how intermediate filaments influence mitochondrial morphology, subcellular localization, and function through direct and indirect interactions and how perturbations of these interactions may lead to human diseases. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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1961 KiB  
Review
Epithelial Intermediate Filaments: Guardians against Microbial Infection?
by Florian Geisler and Rudolf E. Leube
Cells 2016, 5(3), 29; https://doi.org/10.3390/cells5030029 - 27 Jun 2016
Cited by 30 | Viewed by 7486
Abstract
Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about [...] Read more.
Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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12112 KiB  
Review
The Hagfish Gland Thread Cell: A Fiber-Producing Cell Involved in Predator Defense
by Douglas S. Fudge and Sarah Schorno
Cells 2016, 5(2), 25; https://doi.org/10.3390/cells5020025 - 31 May 2016
Cited by 12 | Viewed by 10174
Abstract
Fibers are ubiquitous in biology, and include tensile materials produced by specialized glands (such as silks), extracellular fibrils that reinforce exoskeletons and connective tissues (such as chitin and collagen), as well as intracellular filaments that make up the metazoan cytoskeleton (such as F-actin, [...] Read more.
Fibers are ubiquitous in biology, and include tensile materials produced by specialized glands (such as silks), extracellular fibrils that reinforce exoskeletons and connective tissues (such as chitin and collagen), as well as intracellular filaments that make up the metazoan cytoskeleton (such as F-actin, microtubules, and intermediate filaments). Hagfish gland thread cells are unique in that they produce a high aspect ratio fiber from cytoskeletal building blocks within the confines of their cytoplasm. These threads are elaborately coiled into structures that readily unravel when they are ejected into seawater from the slime glands. In this review we summarize what is currently known about the structure and function of gland thread cells and we speculate about the mechanism that these cells use to produce a mechanically robust fiber that is almost one hundred thousand times longer than it is wide. We propose that a key feature of this mechanism involves the unidirectional rotation of the cell’s nucleus, which would serve to twist disorganized filaments into a coherent thread and impart a torsional stress on the thread that would both facilitate coiling and drive energetic unravelling in seawater. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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1472 KiB  
Review
Role of Intermediate Filaments in Vesicular Traffic
by Azzurra Margiotta and Cecilia Bucci
Cells 2016, 5(2), 20; https://doi.org/10.3390/cells5020020 - 25 Apr 2016
Cited by 44 | Viewed by 15356
Abstract
Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, [...] Read more.
Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, such as the organization of microtubules and microfilaments, the regulation of nuclear structure and activity, the control of cell cycle and the regulation of signal transduction pathways. Furthermore, a number of intermediate filament proteins have been involved in the acquisition of tumorigenic properties. Over the last years, a strong involvement of intermediate filament proteins in the regulation of several aspects of intracellular trafficking has strongly emerged. Here, we review the functions of intermediate filaments proteins focusing mainly on the recent knowledge gained from the discovery that intermediate filaments associate with key proteins of the vesicular membrane transport machinery. In particular, we analyze the current understanding of the contribution of intermediate filaments to the endocytic pathway. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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572 KiB  
Review
Vimentin in Bacterial Infections
by Tim N. Mak and Holger Brüggemann
Cells 2016, 5(2), 18; https://doi.org/10.3390/cells5020018 - 18 Apr 2016
Cited by 50 | Viewed by 13085
Abstract
Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not [...] Read more.
Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection. Full article
(This article belongs to the Special Issue Beyond Cell Mechanics: Novel Functions of Intermediate Filaments)
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