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Cold Spring Harbor Perspectives in... Aug 2016Organisms from all domains of life depend on filaments of the protein actin to provide structure and to support internal movements. Many eukaryotic cells use forces... (Review)
Review
Organisms from all domains of life depend on filaments of the protein actin to provide structure and to support internal movements. Many eukaryotic cells use forces produced by actin polymerization for their motility, and myosin motor proteins use ATP hydrolysis to produce force on actin filaments. Actin polymerizes spontaneously, followed by hydrolysis of a bound adenosine triphosphate (ATP). Dissociation of the γ-phosphate prepares the polymer for disassembly. This review provides an overview of the properties of actin and shows how dozens of proteins control both the assembly and disassembly of actin filaments. These players catalyze nucleotide exchange on actin monomers, initiate polymerization, promote phosphate dissociation, cap the ends of polymers, cross-link filaments to each other and other cellular components, and sever filaments.
Topics: Actins; Adenosine Triphosphate; Animals; Catalysis; Hydrolysis; Polymerization; Protein Binding
PubMed: 26988969
DOI: 10.1101/cshperspect.a018226 -
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 -
Advances in Experimental Medicine and... 2020Directed movements on actin filaments within the cell are powered by molecular motors of the myosin superfamily. On actin filaments, myosin motors convert the energy... (Review)
Review
Directed movements on actin filaments within the cell are powered by molecular motors of the myosin superfamily. On actin filaments, myosin motors convert the energy from ATP into force and movement. Myosin motors power such diverse cellular functions as cytokinesis, membrane trafficking, organelle movements, and cellular migration. Myosin generates force and movement via a number of structural changes associated with hydrolysis of ATP, binding to actin, and release of the ATP hydrolysis products while bound to actin. Herein we provide an overview of those structural changes and how they relate to the actin-myosin ATPase cycle. These structural changes are the basis of chemo-mechanical transduction by myosin motors.
Topics: Actin Cytoskeleton; Actins; Adenosine Triphosphate; Hydrolysis; Movement; Myosins
PubMed: 32451853
DOI: 10.1007/978-3-030-38062-5_2 -
Science (New York, N.Y.) Jun 2020Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers...
Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here, we developed a fluorescent reporter to monitor changes in the density of membrane-proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike the total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration.
Topics: Actins; Cell Membrane; Cell Movement; Cell Polarity; Cell Surface Extensions; Green Fluorescent Proteins; Human Umbilical Vein Endothelial Cells; Humans
PubMed: 32527825
DOI: 10.1126/science.aay7794 -
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 -
Bioengineered Dec 2021Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as a common housekeep gene and used as a reference gene for years. However,...
Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as a common housekeep gene and used as a reference gene for years. However, accumulating evidence indicates that ACTB is abnormally expressed in multiple cancers and hence changes the cytoskeleton to affect the invasiveness and metastasis of tumors. This study aimed to investigate the function and clinical significance of ACTB in pan-cancer. The role of ACTB for prognosis and immune regulation across 33 tumors was explored based on the datasets of gene expression omnibus and the cancer genome atlas. Differential expression of ACTB was found between cancer and adjacent normal tissues, and significant associations was found between ACTB expression and prognosis of tumor patients. In most cancers, ACTB expression was associated with immune cells infiltration, immune checkpoints and other immune modulators. Relevance between ACTB and metastasis and invasion was identified in various types of cancers by CancerSEA. Moreover, focal adhesion and actin regulation-associated pathways were included in the functional mechanisms of ACTB. The expression of ACTB was verified by quantitative real-time polymerase chain reaction. Knockdown of ACTB inhibited head and neck squamous carcinoma cell migration and invasion by NF-κB and Wnt/β-catenin pathways. Our first pan-cancer study of ACTB offers insight into the prognostic and immunological roles of ACTB across different tumors, indicating ACTB may be a potential biomarker for poor prognosis and immune infiltration in cancers, and the role of ACTB as a reference gene in cancers was challenged.
Topics: Actins; Aged; Aged, 80 and over; Cell Line, Tumor; Female; Gene Knockdown Techniques; Humans; Male; Neoplasms; Prognosis; Transcriptome
PubMed: 34486492
DOI: 10.1080/21655979.2021.1973220 -
ELife Feb 2018The differences between β- and γ-actin are deeper than those between the amino acid sequences of these two proteins.
The differences between β- and γ-actin are deeper than those between the amino acid sequences of these two proteins.
Topics: Actins; Amino Acid Sequence
PubMed: 29388551
DOI: 10.7554/eLife.34477 -
Current Biology : CB Aug 2015The growth and migration of neurons require continuous remodelling of the neuronal cytoskeleton, providing a versatile cellular framework for force generation and guided... (Review)
Review
The growth and migration of neurons require continuous remodelling of the neuronal cytoskeleton, providing a versatile cellular framework for force generation and guided movement, in addition to structural support. Actin filaments and microtubules are central to the dynamic action of the cytoskeleton and rapid advances in imaging technologies are enabling ever more detailed visualisation of the dynamic intracellular networks that they form. However, these filaments do not act individually and an expanding body of evidence emphasises the importance of actin-microtubule crosstalk in orchestrating cytoskeletal dynamics. Here, we summarise our current understanding of the structure and dynamics of actin and microtubules in isolation, before reviewing both the mechanisms and the molecular players involved in mediating actin-microtubule crosstalk in neurons.
Topics: Actins; Cytoskeleton; Microtubules; Neurons
PubMed: 26241148
DOI: 10.1016/j.cub.2015.06.020 -
Bioscience Reports Sep 2022Cell homeostasis is maintained in all organisms by the constant adjustment of cell constituents and organisation to account for environmental context. Fine-tuning of the... (Review)
Review
Cell homeostasis is maintained in all organisms by the constant adjustment of cell constituents and organisation to account for environmental context. Fine-tuning of the optimal balance of proteins for the conditions, or protein homeostasis, is critical to maintaining cell homeostasis. Actin, a major constituent of the cytoskeleton, forms many different structures which are acutely sensitive to the cell environment. Furthermore, actin structures interact with and are critically important for the function and regulation of multiple factors involved with mRNA and protein production and degradation, and protein regulation. Altogether, actin is a key, if often overlooked, regulator of protein homeostasis across eukaryotes. In this review, we highlight these roles and how they are altered following cell stress, from mRNA transcription to protein degradation.
Topics: Actin Cytoskeleton; Actins; Cytoskeleton; Homeostasis; Proteostasis; RNA, Messenger
PubMed: 36043949
DOI: 10.1042/BSR20210848 -
Developmental Cell Jun 2016Circular or ring-like actin structures play important roles in various developmental and physiological processes. Commonly, these rings are composed of actin filaments... (Review)
Review
Circular or ring-like actin structures play important roles in various developmental and physiological processes. Commonly, these rings are composed of actin filaments and myosin motors (actomyosin) that, upon activation, trigger ring constriction. Actomyosin ring constriction, in turn, has been implicated in key cellular processes ranging from cytokinesis to wound closure. Non-constricting actin ring-like structures also form at cell-cell contacts, where they exert a stabilizing function. Here, we review recent studies on the formation and function of actin ring-like structures in various morphogenetic processes, shedding light on how those different rings have been adapted to fulfill their specific roles.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Adhesion; Cytokinesis; Humans; Wound Healing
PubMed: 27326928
DOI: 10.1016/j.devcel.2016.05.024