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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 -
Trends in Cell Biology Sep 2020Cell migration is a highly dynamic process driven by the cytoskeleton, which mainly comprises the actin microfilaments, microtubules, and intermediate filaments. During... (Review)
Review
Cell migration is a highly dynamic process driven by the cytoskeleton, which mainly comprises the actin microfilaments, microtubules, and intermediate filaments. During migration, cells polarize and form protrusions at the front, where new adhesions are formed. These nascent adhesions mature into focal adhesions that transmit the traction forces required for movement. All of these steps are coupled to major cytoskeletal rearrangements and are controlled by a wide array of signaling cascades. The constant crosstalk between actin, microtubules, and intermediate filaments ensures their coordinated dynamics to facilitate cell migration. Here, we first describe how master regulators, such as RhoGTPases, can simultaneously control the three cytoskeletal structures. We then summarize the recent crosstalk mechanisms by which cytoskeletal networks can locally regulate one another in order to function in a coordinated and efficient manner during migration.
Topics: Actins; Animals; Biomechanical Phenomena; Cell Adhesion; Cell Movement; Cell Polarity; Cytoskeleton; Humans
PubMed: 32674938
DOI: 10.1016/j.tcb.2020.06.004 -
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 -
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 -
Trends in Cell Biology Mar 2021Actin plays roles in many important cellular processes, including cell motility, organelle movement, and cell signaling. The discovery of transmembrane actin-binding... (Review)
Review
Actin plays roles in many important cellular processes, including cell motility, organelle movement, and cell signaling. The discovery of transmembrane actin-binding proteins at the outer nuclear membrane (ONM) raises the exciting possibility that actin can play a role in direct force transmission to the nucleus and the genome at its interior. Actin-dependent nucleus displacement was first described a decade ago. We are now gaining a more detailed understanding of its mechanisms, as well as new roles for actin during mitosis and meiosis, for gene expression, and in the cell's response to mechanical stimuli. Here we review these recent developments, the actin-binding proteins involved, the tissue specificity of these mechanisms, and methods developed to reconstitute and study this interaction in vitro.
Topics: Actins; Cell Movement; Cell Nucleus; Microfilament Proteins; Nuclear Envelope
PubMed: 33376040
DOI: 10.1016/j.tcb.2020.11.009 -
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 -
Journal of Muscle Research and Cell... Mar 2020The interactions of cytoskeletal actin filaments with myosin family motors are essential for the integrity and function of eukaryotic cells. They support a wide range of... (Review)
Review
The interactions of cytoskeletal actin filaments with myosin family motors are essential for the integrity and function of eukaryotic cells. They support a wide range of force-dependent functions. These include mechano-transduction, directed transcellular transport processes, barrier functions, cytokinesis, and cell migration. Despite the indispensable role of tropomyosins in the generation and maintenance of discrete actomyosin-based structures, the contribution of individual cytoskeletal tropomyosin isoforms to the structural and functional diversification of the actin cytoskeleton remains a work in progress. Here, we review processes that contribute to the dynamic sorting and targeted distribution of tropomyosin isoforms in the formation of discrete actomyosin-based structures in animal cells and their effects on actin-based motility and contractility.
Topics: Actins; Humans; Tropomyosin
PubMed: 31054005
DOI: 10.1007/s10974-019-09514-0 -
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