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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 -
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 -
International Journal of Molecular... Nov 2019Muscular contraction is a fundamental phenomenon in all animals; without it life as we know it would be impossible. The basic mechanism in muscle, including heart... (Review)
Review
Muscular contraction is a fundamental phenomenon in all animals; without it life as we know it would be impossible. The basic mechanism in muscle, including heart muscle, involves the interaction of the protein filaments myosin and actin. Motility in all cells is also partly based on similar interactions of actin filaments with non-muscle myosins. Early studies of muscle contraction have informed later studies of these cellular actin-myosin systems. In muscles, projections on the myosin filaments, the so-called myosin heads or cross-bridges, interact with the nearby actin filaments and, in a mechanism powered by ATP-hydrolysis, they move the actin filaments past them in a kind of cyclic rowing action to produce the macroscopic muscular movements of which we are all aware. In this special issue the papers and reviews address different aspects of the actin-myosin interaction in muscle as studied by a plethora of complementary techniques. The present overview provides a brief and elementary introduction to muscle structure and function and the techniques used to study it. It goes on to give more detailed descriptions of what is known about muscle components and the cross-bridge cycle using structural biology techniques, particularly protein crystallography, electron microscopy and X-ray diffraction. It then has a quick look at muscle mechanics and it summarises what can be learnt about how muscle works based on the other studies covered in the different papers in the special issue. A picture emerges of the main molecular steps involved in the force-producing process; steps that are also likely to be seen in non-muscle myosin interactions with cellular actin filaments. Finally, the remarkable advances made in studying the effects of mutations in the contractile assembly in causing specific muscle diseases, particularly those in heart muscle, are outlined and discussed.
Topics: Actins; Animals; Humans; Models, Biological; Muscle Contraction; Muscle, Striated; Muscles; Myosins; Protein Binding; Sarcomeres; Structure-Activity Relationship
PubMed: 31739584
DOI: 10.3390/ijms20225715 -
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 -
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 -
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 -
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 -
Biomolecules Feb 2023The interface between the cellular actin network and diverse forms of integrin-mediated cell adhesions displays a unique capacity to serve as accurate chemical and... (Review)
Review
The interface between the cellular actin network and diverse forms of integrin-mediated cell adhesions displays a unique capacity to serve as accurate chemical and mechanical sensors of the cell's microenvironment. Focal adhesion-like structures of diverse cell types, podosomes in osteoclasts, and invadopodia of invading cancer cells display distinct morphologies and apparent functions. Yet, all three share a similar composition and mode of coupling between a protrusive structure (the lamellipodium, the core actin bundle of the podosome, and the invadopodia protrusion, respectively), and a nearby adhesion site. Cytoskeletal or external forces, applied to the adhesion sites, trigger a cascade of unfolding and activation of key adhesome components (e.g., talin, vinculin, integrin), which in turn, trigger the assembly of adhesion sites and generation of adhesion-mediated signals that affect cell behavior and fate. The structural and molecular mechanisms underlying the dynamic crosstalk between the actin cytoskeleton and the adhesome network are discussed.
Topics: Actins; Integrins; Cytoskeleton; Cell Adhesion; Actin Cytoskeleton
PubMed: 36830665
DOI: 10.3390/biom13020294