-
Annual Review of Biophysics 2011Actin is the most abundant protein in most eukaryotic cells. It is highly conserved and participates in more protein-protein interactions than any known protein. These... (Review)
Review
Actin is the most abundant protein in most eukaryotic cells. It is highly conserved and participates in more protein-protein interactions than any known protein. These properties, along with its ability to transition between monomeric (G-actin) and filamentous (F-actin) states under the control of nucleotide hydrolysis, ions, and a large number of actin-binding proteins, make actin a critical player in many cellular functions, ranging from cell motility and the maintenance of cell shape and polarity to the regulation of transcription. Moreover, the interaction of filamentous actin with myosin forms the basis of muscle contraction. Owing to its central role in the cell, the actin cytoskeleton is also disrupted or taken over by numerous pathogens. Here we review structures of G-actin and F-actin and discuss some of the interactions that control the polymerization and disassembly of actin.
Topics: Actins; Binding Sites; Computer Simulation; Models, Biological; Models, Chemical; Models, Molecular; Protein Binding; Protein Conformation; Structure-Activity Relationship
PubMed: 21314430
DOI: 10.1146/annurev-biophys-042910-155359 -
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 -
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 -
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 -
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 -
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 -
Nature Nov 2022ATP-hydrolysis-coupled actin polymerization is a fundamental mechanism of cellular force generation. In turn, force and actin filament (F-actin) nucleotide state...
ATP-hydrolysis-coupled actin polymerization is a fundamental mechanism of cellular force generation. In turn, force and actin filament (F-actin) nucleotide state regulate actin dynamics by tuning F-actin's engagement of actin-binding proteins through mechanisms that are unclear. Here we show that the nucleotide state of actin modulates F-actin structural transitions evoked by bending forces. Cryo-electron microscopy structures of ADP-F-actin and ADP-P-F-actin with sufficient resolution to visualize bound solvent reveal intersubunit interfaces bridged by water molecules that could mediate filament lattice flexibility. Despite extensive ordered solvent differences in the nucleotide cleft, these structures feature nearly identical lattices and essentially indistinguishable protein backbone conformations that are unlikely to be discriminable by actin-binding proteins. We next introduce a machine-learning-enabled pipeline for reconstructing bent filaments, enabling us to visualize both continuous structural variability and side-chain-level detail. Bent F-actin structures reveal rearrangements at intersubunit interfaces characterized by substantial alterations of helical twist and deformations in individual protomers, transitions that are distinct in ADP-F-actin and ADP-P-F-actin. This suggests that phosphate rigidifies actin subunits to alter the bending structural landscape of F-actin. As bending forces evoke nucleotide-state dependent conformational transitions of sufficient magnitude to be detected by actin-binding proteins, we propose that actin nucleotide state can serve as a co-regulator of F-actin mechanical regulation.
Topics: Actin Cytoskeleton; Actins; Adenosine Diphosphate; Cryoelectron Microscopy; Microfilament Proteins; Solvents; Machine Learning; Protein Conformation
PubMed: 36289330
DOI: 10.1038/s41586-022-05366-w -
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 -
Cells Jul 2020Podocytes are an integral part of the glomerular filtration barrier, a structure that prevents filtration of large proteins and macromolecules into the urine. Podocyte... (Review)
Review
Podocytes are an integral part of the glomerular filtration barrier, a structure that prevents filtration of large proteins and macromolecules into the urine. Podocyte function is dependent on actin cytoskeleton regulation within the foot processes, structures that link podocytes to the glomerular basement membrane. Actin cytoskeleton dynamics in podocyte foot processes are complex and regulated by multiple proteins and other factors. There are two key signal integration and structural hubs within foot processes that regulate the actin cytoskeleton: the slit diaphragm and focal adhesions. Both modulate actin filament extension as well as foot process mobility. No matter what the initial cause, the final common pathway of podocyte damage is dysregulation of the actin cytoskeleton leading to foot process retraction and proteinuria. Disruption of the actin cytoskeleton can be due to acquired causes or to genetic mutations in key actin regulatory and signaling proteins. Here, we describe the major structural and signaling components that regulate the actin cytoskeleton in podocytes as well as acquired and genetic causes of actin dysregulation.
Topics: Actin Cytoskeleton; Actins; Animals; Disease; Focal Adhesions; Humans; Mutation; Podocytes
PubMed: 32708597
DOI: 10.3390/cells9071700 -
Current Opinion in Cell Biology Feb 2018Actin polymerization provides driving force to aid several types of processes that involve pulling the plasma membrane into the cell, including phagocytosis, cellular... (Review)
Review
Actin polymerization provides driving force to aid several types of processes that involve pulling the plasma membrane into the cell, including phagocytosis, cellular entry of large viruses, and endocytosis. In endocytosis, actin polymerization is especially important under conditions of high membrane tension or high turgor pressure. Recent modeling efforts have shown how actin polymerization can give rise to a distribution of forces around the endocytic site, and explored how these forces affect the shape dynamics; experiments have revealed the structure of the endocytic machinery in increasing detail, and demonstrated key feedback interactions between actin assembly and membrane curvature. Here we provide a perspective on these findings and suggest avenues for future research.
Topics: Actins; Animals; Cell Membrane; Endocytosis; Polymerization; Yeasts
PubMed: 29207306
DOI: 10.1016/j.ceb.2017.11.007