Frontiers in Cytoskeleton Research—From Development to Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (10 December 2019) | Viewed by 55566

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Guest Editor
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Interests: membrane trafficking; neuronal death and regeneration; Sirt1 and aging
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Special Issue Information

Dear Colleagues,

The dynamic cellular cytoskeleton provides shape, rigidity, and motility to all eukaryotic cells. The regulation of cytoskeletal structure, organization, and dynamics underlies a variety of processes including cellular compartmentation, membrane traffic, signaling, and cell division, all of which impact on tissue and organogenesis during development and underpin pathophysiological processes such as wound healing, tissue regeneration, cellular transformation, and formation of intracellular sanctuaries of invasive pathogens.

In this Special Issue of Cells, we invite contributions, in the form of either original research articles or reviews, on aspects related to the theme “Frontiers in Cytoskeleton Research−From Development to Disease”. Articles with mechanistic and functional insights from a cellular or molecular biological perspective are particularly welcome. The manuscripts' content should be broadly relevant to the topics below. Suggestions for other topics would also be welcomed and should be addressed to the editor.

  • Structural and functional aspects of cytoskeletal components—actin, tubulin, microtubules, microfilaments, and intermediate filaments
  • The cytoskeleton and cellular compartmentation—formation of specialized cellular domains such as cilia and axonal segment fence
  • The cytoskeleton in cell division and cell migration
  • The cytoskeleton in embryonic and postnatal development
  • Cytoskeletal changes in cellular transformation and cancer
  • Cytoskeletal changes in cell and tissue regeneration
  • Cytoskeletal changes in intracellular viral and bacterial invasions

Dr. Bor Luen Tang
Guest Editor

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Keywords

  • cytoskeleton
  • actin
  • tubulin
  • intermediate filaments
  • cell migration, regeneration
  • cancer

Published Papers (6 papers)

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Research

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17 pages, 6385 KiB  
Article
Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent
by Mary T. Doolin, Thea S. Ornstein and Kimberly M. Stroka
Cells 2019, 8(5), 427; https://doi.org/10.3390/cells8050427 - 8 May 2019
Cited by 9 | Viewed by 6364
Abstract
Mechanosensing of the mechanical microenvironment by cells regulates cell phenotype and function. The nucleus is critical in mechanosensing, as it transmits external forces from the cellular microenvironment to the nuclear envelope housing chromatin. This study aims to elucidate how mechanical confinement affects nuclear [...] Read more.
Mechanosensing of the mechanical microenvironment by cells regulates cell phenotype and function. The nucleus is critical in mechanosensing, as it transmits external forces from the cellular microenvironment to the nuclear envelope housing chromatin. This study aims to elucidate how mechanical confinement affects nuclear deformation within several cell types, and to determine the role of cytoskeletal elements in controlling nuclear deformation. Human cancer cells (MDA-MB-231), human mesenchymal stem cells (MSCs), and mouse fibroblasts (L929) were seeded within polydimethylsiloxane (PDMS) microfluidic devices containing microchannels of varying cross-sectional areas, and nuclear morphology and volume were quantified via image processing of fluorescent cell nuclei. We found that the nuclear major axis length remained fairly constant with increasing confinement in MSCs and MDA-MB-231 cells, but increased with increasing confinement in L929 cells. Nuclear volume of L929 cells and MSCs decreased in the most confining channels. However, L929 nuclei were much more isotropic in unconfined channels than MSC nuclei. When microtubule polymerization or myosin II contractility was inhibited, nuclear deformation was altered only in MSCs in wide channels. This work informs our understanding of nuclear mechanics in physiologically relevant spaces, and suggests diverging roles of the cytoskeleton in regulating nuclear deformation in different cell types. Full article
(This article belongs to the Special Issue Frontiers in Cytoskeleton Research—From Development to Disease)
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18 pages, 1416 KiB  
Article
Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis
by Martin Kräter, Jiranuwat Sapudom, Nicole Christin Bilz, Tilo Pompe, Jochen Guck and Claudia Claus
Cells 2018, 7(9), 136; https://doi.org/10.3390/cells7090136 - 13 Sep 2018
Cited by 22 | Viewed by 7047
Abstract
The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. [...] Read more.
The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. Real-time deformability cytometry (RT-DC), as a high-throughput platform for the assessment of cell mechanics, revealed a correlation of an increase in cortical filamentous-actin (F-actin) with a higher cellular stiffness. The additional reduction of stress fibers noted for only some RV strains as the most severe actin rearrangement lowered cell stiffness. Furthermore, a reduced collective and single cell migration speed in a wound healing assay was detected in addition to severe changes in cell morphology. The latter was followed by activation of caspase 3/7 as a sign for induction of apoptosis. Our study emphasizes RT-DC technology as a sensitive means to characterize viral cell populations and to implicate alterations of cell mechanical properties with cell functions. These interdependent events are not only promising options to elucidate viral spread and to understand viral pathologies within the infected host. They also contribute to any diseased cell state, as exemplified by RV as a representative agent for cytoskeletal alterations involved in a cytopathological outcome. Full article
(This article belongs to the Special Issue Frontiers in Cytoskeleton Research—From Development to Disease)
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Review

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27 pages, 1162 KiB  
Review
Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors
by Maria Patrizia Somma, Evgeniya N. Andreyeva, Gera A. Pavlova, Claudia Pellacani, Elisabetta Bucciarelli, Julia V. Popova, Silvia Bonaccorsi, Alexey V. Pindyurin and Maurizio Gatti
Cells 2020, 9(6), 1554; https://doi.org/10.3390/cells9061554 - 26 Jun 2020
Cited by 16 | Viewed by 6564
Abstract
Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different [...] Read more.
Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions. Full article
(This article belongs to the Special Issue Frontiers in Cytoskeleton Research—From Development to Disease)
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41 pages, 9552 KiB  
Review
Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders
by Diana C. Muñoz-Lasso, Carlos Romá-Mateo, Federico V. Pallardó and Pilar Gonzalez-Cabo
Cells 2020, 9(2), 358; https://doi.org/10.3390/cells9020358 - 4 Feb 2020
Cited by 67 | Viewed by 11317
Abstract
Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better [...] Read more.
Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders. Full article
(This article belongs to the Special Issue Frontiers in Cytoskeleton Research—From Development to Disease)
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17 pages, 5929 KiB  
Review
Inception Mechanisms of Tunneling Nanotubes
by Mitja Drab, David Stopar, Veronika Kralj-Iglič and Aleš Iglič
Cells 2019, 8(6), 626; https://doi.org/10.3390/cells8060626 - 21 Jun 2019
Cited by 58 | Viewed by 8372
Abstract
Tunneling nanotubes (TNTs) are thin membranous tubes that interconnect cells, representing a novel route of cell-to-cell communication and spreading of pathogens. TNTs form between many cell types, yet their inception mechanisms remain elusive. We review in this study general concepts related to the [...] Read more.
Tunneling nanotubes (TNTs) are thin membranous tubes that interconnect cells, representing a novel route of cell-to-cell communication and spreading of pathogens. TNTs form between many cell types, yet their inception mechanisms remain elusive. We review in this study general concepts related to the formation and stability of membranous tubular structures with a focus on a deviatoric elasticity model of membrane nanodomains. We review experimental evidence that tubular structures initiate from local membrane bending facilitated by laterally distributed proteins or anisotropic membrane nanodomains. We further discuss the numerical results of several theoretical and simulation models of nanodomain segregation suggesting the mechanisms of TNT inception and stability. We discuss the coupling of nanodomain segregation with the action of protruding cytoskeletal forces, which are mostly provided in eukaryotic cells by the polymerization of f-actin, and review recent inception mechanisms of TNTs in relation to motor proteins. Full article
(This article belongs to the Special Issue Frontiers in Cytoskeleton Research—From Development to Disease)
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38 pages, 3177 KiB  
Review
Vimentin Diversity in Health and Disease
by Frida Danielsson, McKenzie Kirsten Peterson, Helena Caldeira Araújo, Franziska Lautenschläger and Annica Karin Britt Gad
Cells 2018, 7(10), 147; https://doi.org/10.3390/cells7100147 - 21 Sep 2018
Cited by 165 | Viewed by 14211
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Frontiers in Cytoskeleton Research—From Development to Disease)
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