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Cold Spring Harbor Perspectives in... Jan 2018The actin cytoskeleton-a collection of actin filaments with their accessory and regulatory proteins-is the primary force-generating machinery in the cell. It can produce... (Review)
Review
The actin cytoskeleton-a collection of actin filaments with their accessory and regulatory proteins-is the primary force-generating machinery in the cell. It can produce pushing (protrusive) forces through coordinated polymerization of multiple actin filaments or pulling (contractile) forces through sliding actin filaments along bipolar filaments of myosin II. Both force types are particularly important for whole-cell migration, but they also define and change the cell shape and mechanical properties of the cell surface, drive the intracellular motility and morphogenesis of membrane organelles, and allow cells to form adhesions with each other and with the extracellular matrix.
Topics: Actin Cytoskeleton; Actins; Animals; Biological Transport; Cell Movement; Humans; Morphogenesis; Muscle Contraction; Myosin Type II; Phagocytosis
PubMed: 29295889
DOI: 10.1101/cshperspect.a018267 -
Physiological Reviews Jan 2014Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment,... (Review)
Review
Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Movement; Humans; Morphogenesis; Tight Junctions
PubMed: 24382887
DOI: 10.1152/physrev.00018.2013 -
Science (New York, N.Y.) Nov 2009The protein actin forms filaments that provide cells with mechanical support and driving forces for movement. Actin contributes to biological processes such as sensing... (Review)
Review
The protein actin forms filaments that provide cells with mechanical support and driving forces for movement. Actin contributes to biological processes such as sensing environmental forces, internalizing membrane vesicles, moving over surfaces, and dividing the cell in two. These cellular activities are complex; they depend on interactions of actin monomers and filaments with numerous other proteins. Here, we present a summary of the key questions in the field and suggest how those questions might be answered. Understanding actin-based biological phenomena will depend on identifying the participating molecules and defining their molecular mechanisms. Comparisons of quantitative measurements of reactions in live cells with computer simulations of mathematical models will also help generate meaningful insights.
Topics: Actin Cytoskeleton; Actins; Animals; Bacterial Physiological Phenomena; Cell Movement; Cell Shape; Cytokinesis; Cytoskeleton; Endocytosis; Organelles
PubMed: 19965462
DOI: 10.1126/science.1175862 -
Nature Nov 2022The dynamic turnover of actin filaments (F-actin) controls cellular motility in eukaryotes and is coupled to changes in the F-actin nucleotide state. It remains unclear...
The dynamic turnover of actin filaments (F-actin) controls cellular motility in eukaryotes and is coupled to changes in the F-actin nucleotide state. It remains unclear how F-actin hydrolyses ATP and subsequently undergoes subtle conformational rearrangements that ultimately lead to filament depolymerization by actin-binding proteins. Here we present cryo-electron microscopy structures of F-actin in all nucleotide states, polymerized in the presence of Mg or Ca at approximately 2.2 Å resolution. The structures show that actin polymerization induces the relocation of water molecules in the nucleotide-binding pocket, activating one of them for the nucleophilic attack of ATP. Unexpectedly, the back door for the subsequent release of inorganic phosphate (P) is closed in all structures, indicating that P release occurs transiently. The small changes in the nucleotide-binding pocket after ATP hydrolysis and P release are sensed by a key amino acid, amplified and transmitted to the filament periphery. Furthermore, differences in the positions of water molecules in the nucleotide-binding pocket explain why Ca-actin shows slower polymerization rates than Mg-actin. Our work elucidates the solvent-driven rearrangements that govern actin filament assembly and aging and lays the foundation for the rational design of drugs and small molecules for imaging and therapeutic applications.
Topics: Actin Cytoskeleton; Actins; Adenosine Triphosphate; Cryoelectron Microscopy; Hydrolysis; Nucleotides; Water; Aging; Magnesium; Calcium; Amino Acids; Phosphates
PubMed: 36289337
DOI: 10.1038/s41586-022-05241-8 -
Current Biology : CB May 2021Robert Insall introduces the cytoskeleton special issue and summarises some recent changes in our view of actin function and regulation.
Robert Insall introduces the cytoskeleton special issue and summarises some recent changes in our view of actin function and regulation.
Topics: Actin Cytoskeleton; Actins; Cytoskeleton; Microtubules
PubMed: 34033777
DOI: 10.1016/j.cub.2021.04.013 -
Journal of Experimental & Clinical... May 2023Disulfidptosis, a new form of cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to the intracellular...
Disulfidptosis, a new form of cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to the intracellular accumulation of disulfides. This discovery will eventually aid in the development of therapeutic strategies against cancer.
Topics: Humans; Apoptosis; Actins; Actin Cytoskeleton; Cell Death; Cytoskeletal Proteins
PubMed: 37259067
DOI: 10.1186/s13046-023-02712-2 -
Cells Dec 2022The shape and load bearing strength of cells are determined by the complex protein network comprising the actin-myosin cytoskeleton [...].
The shape and load bearing strength of cells are determined by the complex protein network comprising the actin-myosin cytoskeleton [...].
Topics: Actins; Cytoskeleton; Actin Cytoskeleton; Myosins
PubMed: 36611802
DOI: 10.3390/cells12010009 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018Microridges are highly distinctive "fingerprint"-patterned structures situated on the outer surface of superficial layer cells of the epithelium. An F-actin-based... (Review)
Review
Microridges are highly distinctive "fingerprint"-patterned structures situated on the outer surface of superficial layer cells of the epithelium. An F-actin-based cytoskeleton is the underlying core structural component of microridges. The basis for much of what is known about microridges has been provided by in vivo and in vitro fish epithelial systems. Nonetheless the microridge literature is quite small, especially when compared with other actin-based cellular structures such as those involved in cell motility. A PubMed search of the terms "Microridges" yields 261 citations from the mid-1970s to the writing of this review. "Microplicae," an alternative name for microridges, and "Actin Microridges" search terms give 204 and 8 references, respectively, in the same time period. By comparison a search of "Lamellipodia" over the same time period yields over 6,400 citations for this important motility structure while a search of the associated "filopodia" results in close to 7,300 articles. Despite the near-ubiquity of microridges in epithelia across species the study of these structures has clearly been neglected. In-depth analysis of microridge molecular composition is very limited while their function remains unclear. This review draws upon information derived from studies of fish as well as mammalian species to provide a more comprehensive view of these structures. The wide-spread distribution of these structures between species and various tissues indicate the microridges have important and common functions in healthy organisms. Conversely, disease conditions may show alterations in microridge structure and function and thus warrant further investigation. Anat Rec, 301:2037-2050, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actins; Animals; Epithelium; Humans
PubMed: 30414250
DOI: 10.1002/ar.23965 -
Journal of Cellular Physiology May 2022Mitochondria perform diverse functions in the cell and their roles during processes such as cell survival, differentiation, and migration are increasingly being... (Review)
Review
Mitochondria perform diverse functions in the cell and their roles during processes such as cell survival, differentiation, and migration are increasingly being appreciated. Mitochondrial and actin cytoskeletal networks not only interact with each other, but this multifaceted interaction shapes their functional dynamics. The interrelation between mitochondria and the actin cytoskeleton extends far beyond the requirement of mitochondrial ATP generation to power actin dynamics, and impinges upon several major aspects of cellular physiology. Being situated at the hub of cell signaling pathways, mitochondrial function can alter the activity of actin regulatory proteins and therefore modulate the processes downstream of actin dynamics such as cellular migration. As we will discuss, this regulation is highly nuanced and operates at multiple levels allowing mitochondria to occupy a strategic position in the regulation of migration, as well as pathological events that rely on aberrant cell motility such as cancer metastasis. In this review, we summarize the crosstalk that exists between mitochondria and actin regulatory proteins, and further emphasize on how this interaction holds importance in cell migration in normal as well as dysregulated scenarios as in cancer.
Topics: Actin Cytoskeleton; Actins; Cell Movement; Humans; Mitochondria; Neoplasms
PubMed: 35342955
DOI: 10.1002/jcp.30729 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018The actin cytoskeleton has long been recognized as a crucial sub-cellular filament system that is responsible for governing fundamental events ranging from cell division...
The actin cytoskeleton has long been recognized as a crucial sub-cellular filament system that is responsible for governing fundamental events ranging from cell division and muscle contraction to whole cell motility and the maintenance of tissue integrity. Consequently, it is not surprising that this network is the focus of over 100,000 different manuscripts. Alterations in the actin cytoskeleton lead to an assortment of diseases and serve as a target for a variety of pathogens. Here we have brought together a collection of primary research articles and reviews that underscore the broad influence this filament system has on organisms. Anat Rec, 301:1986-1990, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Movement; Humans; Microfilament Proteins
PubMed: 30312025
DOI: 10.1002/ar.23960