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Handbook of Experimental Pharmacology 2017Although most people still associate actin mainly with the cytoskeleton, several lines of evidence, with the earliest studies dating back to decades ago, have emphasized... (Review)
Review
Although most people still associate actin mainly with the cytoskeleton, several lines of evidence, with the earliest studies dating back to decades ago, have emphasized the importance of actin also inside the cell nucleus. Actin has been linked to many gene expression processes from gene activation to chromatin remodeling, but also to maintenance of genomic integrity and intranuclear movement of chromosomes and chromosomal loci. Recent advances in visualizing different forms and dynamic properties of nuclear actin have clearly advanced our understanding of the basic concepts by which actin operates in the nucleus. In this chapter we address the different breakthroughs in nuclear actin studies, as well as discuss the regulation nuclear actin and the importance of nuclear actin dynamics in relation to its different nuclear functions. Our aim is to highlight the fact that actin should be considered as an essential component of the cell nucleus, and its nuclear actions should be taken into account also in experiments on cytoplasmic actin networks.
Topics: Actins; Active Transport, Cell Nucleus; Animals; Cell Nucleus; Chromatin Assembly and Disassembly; Cytoskeleton; DNA-Directed RNA Polymerases; Gene Expression; Humans; Transcriptional Activation
PubMed: 27316910
DOI: 10.1007/164_2016_27 -
Biochemistry. Biokhimiia Sep 2014In addition to the intracellular transport of particles (cargo) along microtubules, there are in the cell two actin-based transport systems. In the actomyosin system the... (Review)
Review
In addition to the intracellular transport of particles (cargo) along microtubules, there are in the cell two actin-based transport systems. In the actomyosin system the transport is driven by myosin, which moves the cargo along actin microfilaments. This transport requires the hydrolysis of ATP in the myosin molecule motor domain that induces conformational changes in the molecule resulting in the myosin movement along the actin filament. The other actin-based transport system of the cell does not involve myosin or other motor proteins. This system is based on a unidirectional actin polymerization, which depends on ATP hydrolysis in actin polymers and is initiated by proteins bound to the surface of transported particles. Obligatory components of the actin-based transport are proteins of the WASP/Scar family and a complex of Arp2/3 proteins. Moreover, the actin-based systems often contain dynamin and cortactin. It is known that a system of actin filaments formed on the surface of particles, the so-called "comet-like tail", is responsible for intracellular movements of pathogenic bacteria, micropinocytotic vesicles, clathrin-coated vesicles, and phagosomes. This movement is reproduced in a cell-free system containing extract of Xenopus oocytes. The formation of a comet-like structure capable of transporting vesicles from the plasma membrane into the cell depth has been studied in detail by high performance electron microscopy combined with electron tomography. A similar mechanism provides the movement of vesicles containing membrane rafts enriched with sphingolipids and cholesterol, changes in position of the nuclear spindle at meiosis, and other processes. This review will consider current ideas about actin polymerization and its regulation by actin-binding proteins and show how these mechanisms are realized in the intracellular actin-based vesicular transport system.
Topics: Actins; Animals; Bacteria; Biological Transport; Cytoplasmic Vesicles; Dynamins; Humans; Microtubules; Movement; Polymerization
PubMed: 25385019
DOI: 10.1134/S0006297914090089 -
Seminars in Cell & Developmental Biology Jun 2020The primary cilia is found on the mammalian cell surface where it serves as an antenna for the reception and transmission of a variety of cellular signaling pathways. At... (Review)
Review
The primary cilia is found on the mammalian cell surface where it serves as an antenna for the reception and transmission of a variety of cellular signaling pathways. At its core the cilium is a microtubule-based organelle, but it is clear that its assembly and function are dependent upon the coordinated regulation of both actin and microtubule dynamics. In particular, the discovery that the centrosome is able to act as both a microtubule and actin organizing centre implies that both cytoskeletal networks are acting directly on the process of cilia assembly. In this review, we set our recent results with the formin FHDC1 in the context of current reports that show each stage of ciliogenesis is impacted by changes in actin dynamics. These include direct effects of actin filament assembly on basal body positioning, vesicle trafficking to and entry into the cilium, cilia length, cilia membrane organization and cilia-dependent signaling.
Topics: Actins; Animals; Cilia; Humans
PubMed: 31862221
DOI: 10.1016/j.semcdb.2019.12.005 -
Cytoskeleton (Hoboken, N.J.) Jul 2018Humans express six highly conserved actin isoforms, which differ the most at their N-termini. Actin's N-terminus undergoes co- and post-translational processing unique...
Humans express six highly conserved actin isoforms, which differ the most at their N-termini. Actin's N-terminus undergoes co- and post-translational processing unique among eukaryotic proteins. During translation, the initiator methionine of the two cytoplasmic isoforms is N-terminally acetylated (Nt-acetylated) and that of the four muscle isoforms is removed and the exposed cysteine is Nt-acetylated. Then, an unidentified acetylaminopeptidase post-translationally removes the Ac-Met (or Ac-Cys), and all six isoforms are re-acetylated at the N-terminus. Despite the vital importance of actin for cellular processes ranging from cell motility to organelle trafficking and cell division, the mechanism and functional consequences of Nt-acetylation remained unresolved. Two recent studies significantly advance our understanding of actin Nt-acetylation. Drazic et al. (2018, Proc Natl Acad Sci U S A, 115, 4399-4404) identify actin's dedicated N-terminal acetyltransferase (NAA80/NatH), and demonstrate that Nt-acetylation critically impacts actin assembly in vitro and in cells. NAA80 knockout cells display increased filopodia and lamellipodia formation and accelerated cell motility. In vitro, the absence of Nt-acetylation leads to a decrease in the rates of filament depolymerization and elongation, including formin-induced elongation. Goris et al. (2018, Proc Natl Acad Sci U S A, 115, 4405-4410] describe the structure of Drosophila NAA80 in complex with a peptide-CoA bi-substrate analog mimicking the N-terminus of β-actin. The structure reveals the source of NAA80's specificity for actin's negatively-charged N-terminus. Nt-acetylation neutralizes a positive charge, thus enhancing the overall negative charge of actin's unique N-terminus. Actin's N-terminus is exposed in the filament and influences the interactions of many actin-binding proteins. These advances open the way to understanding the many likely consequences and functional roles of actin Nt-acetylation.
Topics: Acetylation; Actins; Amino Acid Sequence; Animals; Cell Movement; Drosophila; Humans; Isoenzymes; Models, Molecular; N-Terminal Acetyltransferases; Protein Processing, Post-Translational
PubMed: 30084538
DOI: 10.1002/cm.21455 -
Cytoskeleton (Hoboken, N.J.) Dec 2020The actin family is crucial for many cellular processes and in mammals muscle and non-muscle forms exist. The latter group contains cytoplasmic-β-actin and... (Review)
Review
The actin family is crucial for many cellular processes and in mammals muscle and non-muscle forms exist. The latter group contains cytoplasmic-β-actin and cytoplasmic-γ-actin, almost identical in amino acid sequence and with a significant functional overlap. We introduce the properties of the Actb gene and mRNA transcript(s) with main focus on the 3'UTR and its unique features, that is, the zipcode and two polyadenylation sites creating transcripts of different lengths. Several transgenic mouse models with a modified Actb locus have been created. The different mouse models can be divided into three groups; that is, 5' or 3' insertion models, mouse models with loxP sequences around exon 2-3 resulting in deletion the start codon, and models with gene edited Actb sequences that produces γ-actin protein instead of β-actin. Whole body knockouts and, with one exception, insertion models lead to embryonic lethality indicating that the Actb gene or transcripts or translated β-actin are essential. Tissue specific ablation at later developmental stages lead to no, or mild phenotypes, suggesting that the Actb gene or β-actin protein is somewhat dispensable. Gene edited Actb mice that produce γ-actin are viable. This assumes that the nucleotide sequence of Actb is important and not the specific amino acid sequence of the protein it encodes. Upregulation of other actin paralogs was frequently observed upon β-actin ablation and can also engage in the phenotype. For a better understanding, it will be necessary to analyze in current and future models all relevant actin transcripts and protein levels in a standardized and comprehensive way.
Topics: Actins; Animals; Mice; Mice, Transgenic
PubMed: 33249765
DOI: 10.1002/cm.21647 -
International Journal of Molecular... Jul 2021The primary function of the endothelial cells (EC) lining the inner surface of all vessels is to regulate permeability of vascular walls and to control exchange between... (Review)
Review
The primary function of the endothelial cells (EC) lining the inner surface of all vessels is to regulate permeability of vascular walls and to control exchange between circulating blood and tissue fluids of organs. The EC actin cytoskeleton plays a crucial role in maintaining endothelial barrier function. Actin cytoskeleton reorganization result in EC contraction and provides a structural basis for the increase in vascular permeability, which is typical for many diseases. Actin cytoskeleton in non-muscle cells presented two actin isoforms: non-muscle β-cytoplasmic and γ-cytoplasmic actins (β-actins and γ-actins), which are encoded by ACTB and ACTG1 genes, respectively. They are ubiquitously expressed in the different cells in vivo and in vitro and the β/γ-actin ratio depends on the cell type. Both cytoplasmic actins are essential for cell survival, but they perform various functions in the interphase and cell division and play different roles in neoplastic transformation. In this review, we briefly summarize the research results of recent years and consider the features of the cytoplasmic actins: The spatial organization in close connection with their functional activity in different cell types by focusing on endothelial cells.
Topics: Actins; Animals; Cytoplasm; Endothelial Cells; Humans
PubMed: 34360602
DOI: 10.3390/ijms22157836 -
Molecular and Biochemical Parasitology Nov 2022This study aimed to know if alpha terthienyl (α-T) affects E. histolytica viability and to analyze its effect on the actin cytoskeleton. Trophozoites of E. histolytica...
This study aimed to know if alpha terthienyl (α-T) affects E. histolytica viability and to analyze its effect on the actin cytoskeleton. Trophozoites of E. histolytica HM1-IMSS were treated with α-T, then, cell viability and morphology were evaluated using tetrazolium salts and scanning electron microscopy, respectively; while actin filaments (F-actin) were stained with rhodamine-phalloidin, observed by confocal microscopy and quantified by fluorometry. Data showed that α-T inhibited cell viability of trophozoites (IC, 19.43 µg / mL), affected the cell morphology, and increased the F-actin in a dose-dependent manner. Production of reactive oxygen species and RhoA-GTP levels remained normal in α-T-treated amebas. Two inhibitors that affect the organization of the trophozoites cytoskeleton, one that interacts directly with actin, Cytochalasin D (CD), and one that affects the Rho signaling pathway by inhibiting the downstream effector Rock, Y27632, were tested. Y27632 did not affect the increase of polymerized actin observed with α-T, this compound partially ameliorates the potent disrupting effects of CD on actin filaments. Docking results suggest that α-T could be an antagonist of CD for the same interaction zone in actin, however, more studies are needed to define the action mechanism of this compound.
Topics: Animals; Actin Cytoskeleton; Actins; Entamoeba histolytica; Trophozoites
PubMed: 36084901
DOI: 10.1016/j.molbiopara.2022.111512 -
Histochemistry and Cell Biology Nov 2020Actin is a conserved cytoskeletal protein with essential functions. Here, we review the state-of-the-art reagents, tools and methods used to probe actin biology and... (Review)
Review
Actin is a conserved cytoskeletal protein with essential functions. Here, we review the state-of-the-art reagents, tools and methods used to probe actin biology and functions in zebrafish embryo and larvae. We also discuss specific cell types and tissues where the study of actin in zebrafish has provided new insights into its functions.
Topics: Actins; Animals; Zebrafish
PubMed: 33095903
DOI: 10.1007/s00418-020-01932-3 -
The Journal of Cell Biology Oct 2018The actin cytoskeleton provides structural stability and adaptability to the cell. Neuronal dendrites frequently undergo morphological changes by emanating, elongating,...
The actin cytoskeleton provides structural stability and adaptability to the cell. Neuronal dendrites frequently undergo morphological changes by emanating, elongating, and withdrawing branches. However, the knowledge about actin dynamics in dendrites during these processes is limited. By performing in vivo imaging of F-actin markers, we found that F-actin was highly dynamic and heterogeneously distributed in dendritic shafts with enrichment at terminal dendrites. A dynamic F-actin population that we named actin blobs propagated bidirectionally at an average velocity of 1 µm/min. Interestingly, these actin blobs stalled at sites where new dendrites would branch out in minutes. Overstabilization of F-actin by the G15S mutant abolished actin blobs and dendrite branching. We identified the F-actin-severing protein Tsr/cofilin as a regulator of dynamic actin blobs and branching activity. Hence, actin blob localization at future branching sites represents a dendrite-branching mechanism to account for highly diversified dendritic morphology.
Topics: Actins; Amino Acid Substitution; Animals; Dendrites; Drosophila Proteins; Drosophila melanogaster; Mutation, Missense
PubMed: 30042190
DOI: 10.1083/jcb.201711136 -
Canadian Journal of Physiology and... Mar 2015Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of normal pulmonary vascular relaxation at birth. Hypoxia is known to impede postnatal... (Review)
Review
Persistent pulmonary hypertension of the newborn (PPHN) is defined as the failure of normal pulmonary vascular relaxation at birth. Hypoxia is known to impede postnatal disassembly of the actin cytoskeleton in pulmonary arterial myocytes, resulting in elevation of smooth muscle α-actin and γ-actin content in elastic and resistance pulmonary arteries in PPHN compared with age-matched controls. This review examines the original histological characterization of PPHN with attention to cytoskeletal structural remodeling and actin isoform abundance, reviews the existing evidence for understanding the biophysical and biochemical forces at play during neonatal circulatory transition, and specifically addresses the role of the cortical actin architecture, primarily identified as γ-actin, in the transduction of mechanical force in the hypoxic PPHN pulmonary circuit.
Topics: Actins; Animals; Cytoskeleton; Humans; Hypertension, Pulmonary; Infant, Newborn; Protein Isoforms; Protein Multimerization; Pulmonary Artery
PubMed: 25695400
DOI: 10.1139/cjpp-2014-0413