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Genes & Development Apr 2022More than 27 yr ago, the vimentin knockout ( ) mouse was reported to develop and reproduce without an obvious phenotype, implying that this major cytoskeletal protein... (Review)
Review
More than 27 yr ago, the vimentin knockout ( ) mouse was reported to develop and reproduce without an obvious phenotype, implying that this major cytoskeletal protein was nonessential. Subsequently, comprehensive and careful analyses have revealed numerous phenotypes in mice and their organs, tissues, and cells, frequently reflecting altered responses in the recovery of tissues following various insults or injuries. These findings have been supported by cell-based experiments demonstrating that vimentin intermediate filaments (IFs) play a critical role in regulating cell mechanics and are required to coordinate mechanosensing, transduction, signaling pathways, motility, and inflammatory responses. This review highlights the essential functions of vimentin IFs revealed from studies of mice and cells derived from them.
Topics: Animals; Cell Physiological Phenomena; Intermediate Filaments; Mice; Vimentin
PubMed: 35487686
DOI: 10.1101/gad.349358.122 -
Cold Spring Harbor Perspectives in... Apr 2017SUMMARYNeurofilaments (NFs) are unique among tissue-specific classes of intermediate filaments (IFs) in being heteropolymers composed of four subunits (NF-L... (Review)
Review
SUMMARYNeurofilaments (NFs) are unique among tissue-specific classes of intermediate filaments (IFs) in being heteropolymers composed of four subunits (NF-L [neurofilament light]; NF-M [neurofilament middle]; NF-H [neurofilament heavy]; and α-internexin or peripherin), each having different domain structures and functions. Here, we review how NFs provide structural support for the highly asymmetric geometries of neurons and, especially, for the marked radial expansion of myelinated axons crucial for effective nerve conduction velocity. NFs in axons extensively cross-bridge and interconnect with other non-IF components of the cytoskeleton, including microtubules, actin filaments, and other fibrous cytoskeletal elements, to establish a regionally specialized network that undergoes exceptionally slow local turnover and serves as a docking platform to organize other organelles and proteins. We also discuss how a small pool of oligomeric and short filamentous precursors in the slow phase of axonal transport maintains this network. A complex pattern of phosphorylation and dephosphorylation events on each subunit modulates filament assembly, turnover, and organization within the axonal cytoskeleton. Multiple factors, and especially turnover rate, determine the size of the network, which can vary substantially along the axon. NF gene mutations cause several neuroaxonal disorders characterized by disrupted subunit assembly and NF aggregation. Additional NF alterations are associated with varied neuropsychiatric disorders. New evidence that subunits of NFs exist within postsynaptic terminal boutons and influence neurotransmission suggests how NF proteins might contribute to normal synaptic function and neuropsychiatric disease states.
Topics: Animals; Biomarkers; Humans; Intermediate Filaments; Mental Disorders; Neurofilament Proteins; Organelles; Protein Processing, Post-Translational
PubMed: 28373358
DOI: 10.1101/cshperspect.a018309 -
Cells Apr 2019The cytoskeleton of animal cells is one of the most complicated and functionally versatile structures, involved in processes such as endocytosis, cell division,... (Review)
Review
The cytoskeleton of animal cells is one of the most complicated and functionally versatile structures, involved in processes such as endocytosis, cell division, intra-cellular transport, motility, force transmission, reaction to external forces, adhesion and preservation, and adaptation of cell shape. These functions are mediated by three classical cytoskeletal filament types, as follows: Actin, microtubules, and intermediate filaments. The named filaments form a network that is highly structured and dynamic, responding to external and internal cues with a quick reorganization that is orchestrated on the time scale of minutes and has to be tightly regulated. Especially in brain tumors, the cytoskeleton plays an important role in spreading and migration of tumor cells. As the cytoskeletal organization and regulation is complex and many-faceted, this review aims to summarize the findings about cytoskeletal filament types, including substructures formed by them, such as lamellipodia, stress fibers, and interactions between intermediate filaments, microtubules and actin. Additionally, crucial regulatory aspects of the cytoskeletal filaments and the formed substructures are discussed and integrated into the concepts of cell motility. Even though little is known about the impact of cytoskeletal alterations on the progress of glioma, a final point discussed will be the impact of established cytoskeletal alterations in the cellular behavior and invasion of glioma.
Topics: Actins; Animals; Biological Transport; Cell Division; Cell Movement; Cell Shape; Cytoskeleton; Glioma; Humans; Intermediate Filaments; Microtubules; Signal Transduction
PubMed: 31003495
DOI: 10.3390/cells8040362 -
Brain : a Journal of Neurology Feb 2023The advancing validation and exploitation of CSF and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current... (Review)
Review
The advancing validation and exploitation of CSF and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarize the state of the art, future perspectives, but also limitations, of neurofilament light chain protein as a CSF and blood biomarker in several medical fields, including intensive care medicine, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurological impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease-19 pandemic and in normal ageing. Altogether, current data outline a multifaceted applicability of CSF and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.
Topics: Humans; Intermediate Filaments; COVID-19; Nervous System Diseases; Neurofilament Proteins; Biomarkers; Prognosis
PubMed: 36083979
DOI: 10.1093/brain/awac328 -
Current Opinion in Neurobiology Apr 2020Neurofilaments are proteins selectively expressed in the cytoskeleton of neurons, and increased levels are a marker of damage. Elevated neurofilament levels can serve as... (Review)
Review
Neurofilaments are proteins selectively expressed in the cytoskeleton of neurons, and increased levels are a marker of damage. Elevated neurofilament levels can serve as a marker of ongoing disease activity as well as a tool to measure response to therapeutic intervention. The potential utility of neurofilaments has drastically increased as recent advances have made it possible to measure levels in both the cerebrospinal fluid and blood. There is mounting evidence that neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (NfH) are abnormal in a host of neurodegenerative diseases. In this review we examine how both of these proteins behave across diseases and what we know about how these biomarkers relate to in vivo white matter pathology and each other.
Topics: Biomarkers; Cytoskeleton; Intermediate Filaments; Neurofilament Proteins; White Matter
PubMed: 32151970
DOI: 10.1016/j.conb.2020.02.001 -
Brain : a Journal of Neurology Jul 2020Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood.... (Review)
Review
Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration.
Topics: Animals; Biomarkers; Humans; Intermediate Filaments; Nerve Degeneration; Synapses
PubMed: 32408345
DOI: 10.1093/brain/awaa098 -
ELife Apr 2022Mapping intermediate filaments in three dimensions reveals that the organization of these filaments differs across cell types.
Mapping intermediate filaments in three dimensions reveals that the organization of these filaments differs across cell types.
Topics: Cytoskeleton; Intermediate Filaments
PubMed: 35377313
DOI: 10.7554/eLife.78248 -
Cytoskeleton (Hoboken, N.J.) Apr 2021The cytoskeleton plays important roles in many essential processes at the cellular and organismal levels, including cell migration and motility, cell division, and the... (Review)
Review
The cytoskeleton plays important roles in many essential processes at the cellular and organismal levels, including cell migration and motility, cell division, and the establishment and maintenance of cell and tissue architecture. In order to facilitate these varied functions, the main cytoskeletal components-microtubules, actin filaments, and intermediate filaments-must form highly diverse intracellular arrays in different subcellular areas and cell types. The question of how this diversity is conferred has been the focus of research for decades. One key mechanism is the addition of posttranslational modifications (PTMs) to the major cytoskeletal proteins. This posttranslational addition of various chemical groups dramatically increases the complexity of the cytoskeletal proteome and helps facilitate major global and local cytoskeletal functions. Cytoskeletal proteins undergo many PTMs, most of which are not well understood. Recent technological advances in proteomics and cell biology have allowed for the in-depth study of individual PTMs and their functions in the cytoskeleton. Here, we provide an overview of the major PTMs that occur on the main structural components of the three cytoskeletal systems-tubulin, actin, and intermediate filament proteins-and highlight the cellular function of these modifications.
Topics: Cytoskeletal Proteins; Cytoskeleton; Intermediate Filaments; Microtubules; Protein Processing, Post-Translational
PubMed: 34152688
DOI: 10.1002/cm.21679 -
ASN Neuro 2020Fifty years have passed since the discovery of glial fibrillary acidic protein (GFAP) by Lawrence Eng and colleagues. Now recognized as a member of the intermediate... (Review)
Review
Fifty years have passed since the discovery of glial fibrillary acidic protein (GFAP) by Lawrence Eng and colleagues. Now recognized as a member of the intermediate filament family of proteins, it has become a subject for study in fields as diverse as structural biology, cell biology, gene expression, basic neuroscience, clinical genetics and gene therapy. This review covers each of these areas, presenting an overview of current understanding and controversies regarding GFAP with the goal of stimulating continued study of this fascinating protein.
Topics: Alexander Disease; Animals; Astrocytes; Cloning, Molecular; Glial Fibrillary Acidic Protein; Humans; Intermediate Filaments; Time Factors
PubMed: 32811163
DOI: 10.1177/1759091420949680 -
International Journal of Molecular... May 2022We would like to make readers of the second edition of the Special Issue from the on the Recent Advances in Intermediate Filaments aware of the content of the first...
We would like to make readers of the second edition of the Special Issue from the on the Recent Advances in Intermediate Filaments aware of the content of the first edition on this same topic [...].
Topics: Cytoskeleton; Intermediate Filaments
PubMed: 35628119
DOI: 10.3390/ijms23105308