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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 -
Cells Mar 2023Since the discovery of their role in the regulation of actin cytoskeleton 30 years ago, Rho GTPases have taken center stage in cell motility research [...].
Since the discovery of their role in the regulation of actin cytoskeleton 30 years ago, Rho GTPases have taken center stage in cell motility research [...].
Topics: rho GTP-Binding Proteins; Actin Cytoskeleton; Cell Movement
PubMed: 36899915
DOI: 10.3390/cells12050779 -
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 -
Pediatric Nephrology (Berlin, Germany) Sep 2021The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells,... (Review)
Review
The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells, the glomerular basement membrane, and podocytes. Functional impairment or injury of any of these three components can lead to proteinuria. Podocytes are injured in many forms of human and experimental glomerular disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetes mellitus. One of the earliest signs of podocyte injury is loss of their distinct structure, which is driven by dysregulated dynamics of the actin cytoskeleton. The status of the actin cytoskeleton in podocytes depends on a set of actin binding proteins, nucleators and inhibitors of actin polymerization, and regulatory GTPases. Mutations that alter protein function in each category have been implicated in glomerular diseases in humans and animal models. In addition, a growing body of studies suggest that pharmacological modifications of the actin cytoskeleton have the potential to become novel therapeutics for podocyte-dependent chronic kidney diseases. This review presents an overview of the essential proteins that establish actin cytoskeleton in podocytes and studies demonstrating the feasibility of drugging actin cytoskeleton in kidney diseases.
Topics: Actin Cytoskeleton; Animals; Humans; Podocytes
PubMed: 33188449
DOI: 10.1007/s00467-020-04812-z -
Neurochemical Research Mar 2020Myelinating cells of both the peripheral and central nervous systems (CNSs) undergo dramatic cytoskeletal reorganization in order to differentiate and produce myelin.... (Review)
Review
Myelinating cells of both the peripheral and central nervous systems (CNSs) undergo dramatic cytoskeletal reorganization in order to differentiate and produce myelin. Myelinating oligodendrocytes in the CNS show a periodic actin pattern, demonstrating tight regulation of actin. Furthermore, recent data demonstrate that actin polymerization drives early cell differentiation and that actin depolymerization drives myelin wrapping. Dysregulation of the actin cytoskeleton in myelinating cells is seen in some disease states. This review highlights the cytoskeletal molecules that regulate differentiation of and myelination by cells of the PNS and CNS, informing our understanding of neural development, in particular myelination.
Topics: Actin Cytoskeleton; Animals; Cell Differentiation; Central Nervous System; Humans; Myelin Sheath; Oligodendroglia
PubMed: 30847860
DOI: 10.1007/s11064-019-02753-0 -
Journal of Cell Science May 2021Dynamic remodeling of the actin cytoskeleton is an essential feature for virtually all actin-dependent cellular processes, including cell migration, cell cycle... (Review)
Review
Dynamic remodeling of the actin cytoskeleton is an essential feature for virtually all actin-dependent cellular processes, including cell migration, cell cycle progression, chromatin remodeling and gene expression, and even the DNA damage response. An altered actin cytoskeleton is a structural hallmark associated with numerous pathologies ranging from cardiovascular diseases to immune disorders, neurological diseases and cancer. The actin cytoskeleton in cells is regulated through the orchestrated actions of a myriad of actin-binding proteins. In this Review, we provide a brief overview of the structure and functions of the actin-monomer-binding protein profilin-1 (Pfn1) and then discuss how dysregulated expression of Pfn1 contributes to diseases associated with the cardiovascular system.
Topics: Actin Cytoskeleton; Actins; Cardiovascular Diseases; Humans; Microfilament Proteins; Profilins
PubMed: 33961053
DOI: 10.1242/jcs.249060 -
Small GTPases 2021Cell invasion is associated with numerous patho-physiologic states including cell development and metastatic dissemination. This process couples the activation of cell... (Review)
Review
Cell invasion is associated with numerous patho-physiologic states including cell development and metastatic dissemination. This process couples the activation of cell motility with the capacity to degrade the extracellular matrix, thereby permitting cells to pass through basal membranes. Invasion is sustained by the actions of invadosomes, an ensemble of subcellular structures with high functional homology. Invadosomes are 3D acto-adhesive structures that can also mediate local extracellular matrix degradation through the controlled delivery of proteases. Intracellular RHO GTPases play a central role in the regulation of invadosomes where their complex interplay regulates multiple invadosome functions. This review aims to provide an overview of the synergistic activities of the small GTPases in invadosome biology. This broad-based review also reinforces the importance of the spatiotemporal regulation of small GTPases and the impact of this process on invadosome dynamics.
Topics: Actin Cytoskeleton; Animals; Cell Movement; Extracellular Matrix; Humans; Monomeric GTP-Binding Proteins; Podosomes
PubMed: 33487105
DOI: 10.1080/21541248.2021.1877081 -
Current Opinion in Cell Biology Oct 2018The actin cytoskeleton is the primary force-generating machinery in the cell, which can produce pushing (protrusive) forces using energy of actin polymerization and... (Review)
Review
The actin cytoskeleton is the primary force-generating machinery in the cell, which can produce pushing (protrusive) forces using energy of actin polymerization and pulling (contractile) forces via sliding of bipolar filaments of myosin II along actin filaments, as well as perform other key functions. These functions are essential for whole cell migration, cell interaction with the environment, mechanical properties of the cell surface and other key aspects of cell physiology. The actin cytoskeleton is a highly complex and dynamic system of actin filaments organized into various superstructures by multiple accessory proteins. High resolution architecture of functionally distinct actin arrays provides key clues for understanding actin cytoskeleton functions. This review summarizes recent advance in our understanding of the actin cytoskeleton ultrastructure.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Surface Extensions; Cytokinesis; Humans; Models, Biological; Stress Fibers
PubMed: 29477121
DOI: 10.1016/j.ceb.2018.02.007 -
Current Biology : CB Aug 2014
Topics: Actin Cytoskeleton; Cell Biology; France; History, 20th Century; History, 21st Century; Molecular Biology; Morphogenesis; United States
PubMed: 25237695
DOI: 10.1016/j.cub.2014.06.007 -
International Journal of Molecular... Oct 2021The plasma membrane protects the eukaryotic cell from its surroundings and is essential for cell viability; thus, it is crucial that membrane disruptions are repaired... (Review)
Review
The plasma membrane protects the eukaryotic cell from its surroundings and is essential for cell viability; thus, it is crucial that membrane disruptions are repaired quickly to prevent immediate dyshomeostasis and cell death. Accordingly, cells have developed efficient repair mechanisms to rapidly reseal ruptures and reestablish membrane integrity. The cortical actin cytoskeleton plays an instrumental role in both plasma membrane resealing and restructuring in response to damage. Actin directly aids membrane repair or indirectly assists auxiliary repair mechanisms. Studies investigating single-cell wound repair have often focused on the recruitment and activation of specialized repair machinery, despite the undeniable need for rapid and dynamic cortical actin modulation; thus, the role of the cortical actin cytoskeleton during wound repair has received limited attention. This review aims to provide a comprehensive overview of membrane repair mechanisms directly or indirectly involving cortical actin cytoskeletal remodeling.
Topics: Actin Cytoskeleton; Animals; Cell Membrane; Cell Physiological Phenomena; Humans; Single-Cell Analysis; Wound Healing
PubMed: 34639226
DOI: 10.3390/ijms221910886