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Current Opinion in Cell Biology Feb 2019While it is long known that actin is part of the nuclear proteome, its properties and functions as regulated, functional and dynamically assembled actin filaments are... (Review)
Review
While it is long known that actin is part of the nuclear proteome, its properties and functions as regulated, functional and dynamically assembled actin filaments are only recently emerging. Thus, newly uncovered roles for intranuclear actin filaments are opening new perspectives on how the nucleus and its genomic content may be organized in particular with regard to a given stage of the cell cycle. Here, we summarize recent studies on actin filament polymerization and turnover within the nuclear compartment of mammalian cells. We emphasize and discuss novel findings, in which transient and dynamic nuclear actin filaments have been visualized in physiological contexts, and focus on aspects of signalling mechanisms, chromatin reorganization and DNA repair. Further, a better understanding of the spatiotemporal control of nuclear actin-regulating factors in mammalian cells will ultimately provide a more detailed view on how the nuclear F-actin cytoskeleton contributes to genome organization and nuclear architecture.
Topics: Actin Cytoskeleton; Animals; Cell Cycle; Cell Nucleus; Cell Physiological Phenomena; Cytoskeleton; Microfilament Proteins
PubMed: 30193156
DOI: 10.1016/j.ceb.2018.08.005 -
The EMBO Journal Apr 2021The identification of Tunneling Nanotubes (TNTs) and TNT-like structures signified a critical turning point in the field of cell-cell communication. With hypothesized... (Review)
Review
The identification of Tunneling Nanotubes (TNTs) and TNT-like structures signified a critical turning point in the field of cell-cell communication. With hypothesized roles in development and disease progression, TNTs' ability to transport biological cargo between distant cells has elevated these structures to a unique and privileged position among other mechanisms of intercellular communication. However, the field faces numerous challenges-some of the most pressing issues being the demonstration of TNTs in vivo and understanding how they form and function. Another stumbling block is represented by the vast disparity in structures classified as TNTs. In order to address this ambiguity, we propose a clear nomenclature and provide a comprehensive overview of the existing knowledge concerning TNTs. We also discuss their structure, formation-related pathways, biological function, as well as their proposed role in disease. Furthermore, we pinpoint gaps and dichotomies found across the field and highlight unexplored research avenues. Lastly, we review the methods employed to date and suggest the application of new technologies to better understand these elusive biological structures.
Topics: Actin Cytoskeleton; Animals; Cell Communication; Cell Surface Extensions; Humans; Nanotubes
PubMed: 33646572
DOI: 10.15252/embj.2020105789 -
The FEBS Journal Mar 2021Fascin is an F-actin-bundling protein that cross-links individual actin filaments into straight and stiff bundles. Fascin overexpression in cancer is strongly associated... (Review)
Review
Fascin is an F-actin-bundling protein that cross-links individual actin filaments into straight and stiff bundles. Fascin overexpression in cancer is strongly associated with poor prognosis and metastatic progression across different cancer types. It is well established that fascin plays a causative role in promoting metastatic progression. We will review the recent progress in our understanding of mechanisms underlying fascin-mediated cancer metastasis. This review will cover the biochemical basis for fascin-bundling activity, the mechanisms by which cancer cells upregulate fascin expression and the mechanism underlying fascin-mediated cancer cell migration, invasion, and metastatic colonization. We propose that fascin has broad roles in both metastatic dissemination and metastatic colonization. Understanding these mechanisms will be crucial to the development of anti-metastasis therapeutics targeting fascin.
Topics: Actin Cytoskeleton; Actins; Animals; Carrier Proteins; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Microfilament Proteins; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Neoplastic Cells, Circulating; Protein Isoforms; Signal Transduction; Transcription, Genetic; Tumor Microenvironment
PubMed: 32657526
DOI: 10.1111/febs.15484 -
FEBS Letters Nov 2018The actin cytoskeleton and Rho GTPase signaling to actin assembly are prime targets of bacterial and viral pathogens, simply because actin is involved in all motile and... (Review)
Review
The actin cytoskeleton and Rho GTPase signaling to actin assembly are prime targets of bacterial and viral pathogens, simply because actin is involved in all motile and membrane remodeling processes, such as phagocytosis, macropinocytosis, endocytosis, exocytosis, vesicular trafficking and membrane fusion events, motility, and last but not least, autophagy. This article aims at providing an overview of the most prominent pathogen-induced or -hijacked actin structures, and an outlook on how future research might uncover additional, equally sophisticated interactions.
Topics: Actin Cytoskeleton; Autophagy; Bacteria; Cell Membrane; Host-Pathogen Interactions; Humans; Signal Transduction; Virulence; Viruses
PubMed: 29935019
DOI: 10.1002/1873-3468.13173 -
Journal of Plant Research Mar 2017ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein among eukaryotes. The main function of ADF is the severing and depolymerizing filamentous actin (F-actin), thus... (Review)
Review
ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein among eukaryotes. The main function of ADF is the severing and depolymerizing filamentous actin (F-actin), thus regulating F-actin organization and dynamics and contributing to growth and development of the organisms. Mammalian genomes contain only a few ADF genes, whereas angiosperm plants have acquired an expanding number of ADFs, resulting in the differentiation of physiological functions. Recent studies have revealed functions of ADFs in plant growth and development, and various abiotic and biotic stress responses. In biotic stress responses, ADFs are involved in both susceptibility and resistance, depending on the pathogens. Furthermore, recent studies have highlighted a new role of ADF in the nucleus, possibly in the regulation of gene expression. In this review, I will summarize the current status of plant ADF research and discuss future research directions.
Topics: Actin Cytoskeleton; Destrin; Plant Proteins; Plants
PubMed: 28044231
DOI: 10.1007/s10265-016-0899-8 -
Proceedings of the National Academy of... Jul 2019The tracheary system of plant leaves is composed of a cellulose skeleton with diverse hierarchical structures. It is built of polygonally bent helical microfilaments of...
The tracheary system of plant leaves is composed of a cellulose skeleton with diverse hierarchical structures. It is built of polygonally bent helical microfilaments of cellulose-based nanostructures coated by different layers, which provide them high compression resistance, elasticity, and roughness. Their function includes the transport of water and nutrients from the roots to the leaves. Unveiling details about local interactions of tracheary elements with surrounding material, which varies between plants due to adaptation to different environments, is crucial for understanding ascending fluid transport and for tracheary mechanical strength relevant to potential applications. Here we show that plant tracheary microfilaments, collected from and leaves, have different surface morphologies, revealed by nematic liquid crystal droplets. This results in diverse interactions among microfilaments and with the environment; the differences translate to diverse mechanical properties of entangled microfilaments and their potential applications. The presented study also introduces routes for accurate characterization of plants' microfilaments.
Topics: Actin Cytoskeleton; Amaryllidaceae; Biomechanical Phenomena; Nanostructures; Ornithogalum; Plant Leaves; Plants; Xylem
PubMed: 31196953
DOI: 10.1073/pnas.1901118116 -
The Journal of Medical Investigation :... 2017The adherens junction (AJ) is a cadherin-based and actin filament associated cell-to-cell junction. AJs can contribute to tissue morphogenesis and homeostasis and their... (Review)
Review
The adherens junction (AJ) is a cadherin-based and actin filament associated cell-to-cell junction. AJs can contribute to tissue morphogenesis and homeostasis and their association with actin filaments is crucial for the functions. There are three types of AJs in terms of the mode of actin filament/AJ association. Among many actin-binding proteins associated with AJs, α-catenin is one of the most important actin filament/AJ linkers that functions in all types of AJs. Although α-catenin in cadherin-catenin complex appears to bind to actin filaments within cells, it fails to bind to actin filaments in vitro mysteriously. Recent report revealed that α-catenin in the complex can bind to actin filaments in vitro when forces are applied to the filament. In addition to force-sensitive vinculin binding, α-catenin has another force-sensitive property of actin filament-binding. Elucidation of its significance and the molecular mechanism is indispensable for understanding AJ formation and maintenance during tissue morphogenesis, function and repair. J. Med. Invest. 64: 14-19, February, 2017.
Topics: Actin Cytoskeleton; Actins; Adherens Junctions; Animals; Humans; Protein Binding; Protein Interaction Domains and Motifs; alpha Catenin
PubMed: 28373611
DOI: 10.2152/jmi.64.14 -
International Journal of Molecular... Mar 2022Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure... (Review)
Review
Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure about forty years ago. Since then, it has been revealed as a key protein with functions in a variety of fields including cell migration, survival, and signal transduction, as well as functioning as a structural component. Ezrin acts as a cross-linker of membrane proteins or phospholipids in the plasma membrane and the actin cytoskeleton. It also functions as a platform for signaling molecules at the cell surface. Moreover, ezrin is regarded as an important target protein in cancer diagnosis and therapy because it is a key protein involved in cancer progression and metastasis, and its high expression is linked to poor survival in many cancers. Small molecule inhibitors of ezrin have been developed and investigated as candidate molecules that suppress cancer metastasis. Here, we wish to comprehensively review the roles of ezrin from the pathophysiological points of view.
Topics: Actin Cytoskeleton; Actins; Cell Membrane; Cytoskeletal Proteins; Microfilament Proteins; Phosphoproteins
PubMed: 35328667
DOI: 10.3390/ijms23063246 -
International Journal of Molecular... Feb 2022Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which... (Review)
Review
Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.
Topics: Actin Cytoskeleton; Actins; Carcinogenesis; Cell Movement; Humans; Microfilament Proteins; Small Molecule Libraries
PubMed: 35216237
DOI: 10.3390/ijms23042118 -
Trends in Cell Biology Oct 2014The actin cytoskeleton assembles into branched networks or bundles to generate mechanical force for critical cellular processes such as establishment of polarity,... (Review)
Review
The actin cytoskeleton assembles into branched networks or bundles to generate mechanical force for critical cellular processes such as establishment of polarity, adhesion, and migration. Stress fibers (SFs) are contractile actomyosin structures that physically couple to the extracellular matrix through integrin-based focal adhesions (FAs), thereby transmitting force into and across the cell. Recently, LIN-11, Isl1, and MEC-3 (LIM) domain proteins have been implicated in mediating this cytoskeletal mechanotransduction. Among the more well-studied LIM domain adapter proteins is zyxin, a dynamic component of both FAs and SFs. Here we discuss recent research detailing the mechanisms by which SFs adjust their structure and composition to balance mechanical forces and suggest ways that zyxin and other LIM domain proteins mediate mechanoresponse.
Topics: Actin Cytoskeleton; Animals; Humans; LIM-Homeodomain Proteins; Mechanotransduction, Cellular; Stress, Mechanical
PubMed: 24933506
DOI: 10.1016/j.tcb.2014.04.009