-
Biology of the Cell Apr 2023The human immunodeficiency virus type 1 (HIV-1) is an intracellular pathogen whose replication cycle strictly depends on the host cell molecular machinery. HIV-1 crosses... (Review)
Review
The human immunodeficiency virus type 1 (HIV-1) is an intracellular pathogen whose replication cycle strictly depends on the host cell molecular machinery. HIV-1 crosses twice the plasma membrane, to get in and to get out of the cell. Therefore, the first and the last line of intracellular component encountered by the virus is the cortical actin network. Here, we review the role of actin and actin-related proteins in HIV-1 entry, assembly, budding, and release. We first highlight the mechanisms controlling actin polymerization at the entry site that promote the clustering of HIV-1 receptors, a crucial step for the virus to fuse with the plasma membrane. Then, we describe how actin is transiently depolymerized locally to allow the capsid to cross the actin cortex, before migrating towards the nucleus. Finally, we review the role of several actin-binding proteins in actin remodeling events required for membrane deformation and curvature at the viral assembly site as well as for virus release. Strikingly, it appears that common actin-regulating pathways are involved in viral entry and exit. However, while the role of actin remodeling during entry is well understood, this is not the case during exit. We discuss remaining challenges regarding the actin-dependent mechanisms involved in HIV-1 entry and exit, and how they could be overcome.
Topics: Humans; Actins; HIV-1; Actin Cytoskeleton; Cell Line; Cell Membrane
PubMed: 36597754
DOI: 10.1111/boc.202200085 -
Biochemical Pharmacology Aug 2023Cellular actin dynamic is controlled by a plethora of actin binding proteins (ABPs), including actin nucleating, bundling, cross-linking, capping, and severing proteins.... (Review)
Review
Cellular actin dynamic is controlled by a plethora of actin binding proteins (ABPs), including actin nucleating, bundling, cross-linking, capping, and severing proteins. In this review, regulation of actin dynamics by ABPs will be introduced, and the role of the F-actin severing protein cofilin-1 and the F-actin bundling protein L-plastin in actin dynamics discussed in more detail. Since up-regulation of these proteins in different kinds of cancers is associated with malignant progression of cancer cells, we suggest the cryogenic electron microscopy (Cryo-EM) structure of F- actin with the respective ABP as template for in silico drug design to specifically disrupt the interaction of these ABPs with F-actin.
Topics: Actins; Cryoelectron Microscopy; Microfilament Proteins; Actin Cytoskeleton; Drug Discovery; Protein Binding
PubMed: 37399949
DOI: 10.1016/j.bcp.2023.115680 -
ELife Feb 2023Actin isoforms organize into distinct networks that are essential for the normal function of eukaryotic cells. Despite a high level of sequence and structure...
Actin isoforms organize into distinct networks that are essential for the normal function of eukaryotic cells. Despite a high level of sequence and structure conservation, subtle differences in their design principles determine the interaction with myosin motors and actin-binding proteins. Therefore, identifying how the structure of actin isoforms relates to function is important for our understanding of normal cytoskeletal physiology. Here, we report the high-resolution structures of filamentous skeletal muscle α-actin (3.37 Å), cardiac muscle α-actin (3.07 Å), ß-actin (2.99 Å), and γ-actin (3.38 Å) in the Mg·ADP state with their native post-translational modifications. The structures revealed isoform-specific conformations of the N-terminus that shift closer to the filament surface upon myosin binding, thereby establishing isoform-specific interfaces. Collectively, the structures of single-isotype, post-translationally modified bare skeletal muscle α-actin, cardiac muscle α-actin, ß-actin, and γ-actin reveal general principles, similarities, and differences between isoforms. They complement the repertoire of known actin structures and allow for a comprehensive understanding of in vitro and in vivo functions of actin isoforms.
Topics: Actins; Protein Isoforms; Myosins; Muscle, Skeletal; Actin Cytoskeleton
PubMed: 36790143
DOI: 10.7554/eLife.82015 -
Current Opinion in Cell Biology Feb 2021The origin of the eukaryotic cell is one of the greatest mysteries in modern biology. Eukaryotic-wide specific biological processes arose in the lost ancestors of... (Review)
Review
The origin of the eukaryotic cell is one of the greatest mysteries in modern biology. Eukaryotic-wide specific biological processes arose in the lost ancestors of eukaryotes. These distinctive features, such as the actin cytoskeleton, define what it is to be a eukaryote. Recent sequencing, characterization, and isolation of Asgard archaea have opened an intriguing window into the pre-eukaryotic cell. Firstly, sequencing of anaerobic sediments identified a group of uncultured organisms, Asgard archaea, which contain genes with homology to eukaryotic signature genes. Secondly, characterization of the products of these genes at the protein level demonstrated that Asgard archaea have related biological processes to eukaryotes. Finally, the isolation of an Asgard archaeon has produced a model organism in which the morphological consequences of the eukaryotic-like processes can be studied. Here, we consider the consequences for the Asgard actin cytoskeleton and for the evolution of a regulated actin system in the archaea-to-eukaryotic transition.
Topics: Actin Cytoskeleton; Actins; Animals; Archaea; Archaeal Proteins; Biological Evolution; Eukaryota; Eukaryotic Cells; Humans; Metagenomics; Phylogeny; Sequence Analysis, Protein
PubMed: 33049465
DOI: 10.1016/j.ceb.2020.08.011 -
The Journal of Medical Investigation :... 2017The adherens junction (AJ) is a cadherin-based and actin filament associated cell-to-cell junction. AJs can contribute to tissue morphogenesis and homeostasis and their... (Review)
Review
The adherens junction (AJ) is a cadherin-based and actin filament associated cell-to-cell junction. AJs can contribute to tissue morphogenesis and homeostasis and their association with actin filaments is crucial for the functions. There are three types of AJs in terms of the mode of actin filament/AJ association. Among many actin-binding proteins associated with AJs, α-catenin is one of the most important actin filament/AJ linkers that functions in all types of AJs. Although α-catenin in cadherin-catenin complex appears to bind to actin filaments within cells, it fails to bind to actin filaments in vitro mysteriously. Recent report revealed that α-catenin in the complex can bind to actin filaments in vitro when forces are applied to the filament. In addition to force-sensitive vinculin binding, α-catenin has another force-sensitive property of actin filament-binding. Elucidation of its significance and the molecular mechanism is indispensable for understanding AJ formation and maintenance during tissue morphogenesis, function and repair. J. Med. Invest. 64: 14-19, February, 2017.
Topics: Actin Cytoskeleton; Actins; Adherens Junctions; Animals; Humans; Protein Binding; Protein Interaction Domains and Motifs; alpha Catenin
PubMed: 28373611
DOI: 10.2152/jmi.64.14 -
Journal of Experimental Botany Jun 2017The eukaryotic actin cytoskeleton is a highly dynamic framework that is involved in many biological processes, such as cell growth, division, morphology, and motility.... (Review)
Review
The eukaryotic actin cytoskeleton is a highly dynamic framework that is involved in many biological processes, such as cell growth, division, morphology, and motility. G-actin polymerizes into microfilaments that associate into bundles, patches, and networks, which, in turn, organize into higher order structures that are fundamental for the course of important physiological events. Actin rings are an example for such higher order actin entities, but this term represents an actually diverse set of subcellular structures that are involved in various processes. This review especially sheds light on a crucial type of non-constricting ring-like actin networks, and categorizes them under the term 'actin fringe'. These 'actin fringes' are visualized as highly dynamic and yet steady structures in the tip of various polarized growing cells. The present comprehensive overview compares the actin fringe characteristics of rapidly elongating pollen tubes with several related actin arrays in other cell types of diverse species. The current state of knowledge about various actin fringe functions is summarized, and the key role of this structure in the polar growth process is discussed.
Topics: Actin Cytoskeleton; Actins; Plant Development; Polar Bodies; Pollen Tube
PubMed: 28859380
DOI: 10.1093/jxb/erx195 -
Histology and Histopathology Nov 2017Actin is highly conserved and it is the most widespread protein in eukaryotic cells. One of the most important features of actin, which allows it to have many different... (Review)
Review
Actin is highly conserved and it is the most widespread protein in eukaryotic cells. One of the most important features of actin, which allows it to have many different functions, is its ability to polymerize and interact with many other proteins. Actins are the major constituent of the actin cytoskeleton, which is an important system that is involved in various aspects of cell function, including cell motility, structure, integrity, regulation of signal transduction and transcription. Six mammal actin isoforms are highly conserved and share common functions. Two of them, β and γ non-muscle actin isoforms, which differ only by four amino acids located at the N-terminus of the polypeptide chain, are required for survival and proper cell functioning. We also summarized data about actbl2, which is suggested to be a newly discovered isoactin. Here, we review the current knowledge about tissue-specific expression of the non-muscle actin isoforms and possible functional differences between them. We also discuss molecular tools, which in recent years have allowed for a better understanding of the role of these proteins in cell functioning.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Movement; Humans; Protein Isoforms
PubMed: 28439872
DOI: 10.14670/HH-11-896 -
Cold Spring Harbor Perspectives in... Aug 2022Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix... (Review)
Review
Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix molecules regulated by the actin cytoskeleton. This microscopic network of filaments is present within the cytoplasm of all cells and provides the shape and mechanical support required for cell movement and proliferation. Here, an overview of the processes of wound healing are described from the perspective of the cell in relation to the actin cytoskeleton. Key points of discussion include the role of actin, its binding proteins, signaling pathways, and events that play significant roles in the phases of wound healing. The identification of cytoskeletal targets that can be used to manipulate and improve wound healing is included as an emerging area of focus that may inform future therapeutic approaches to improve healing of complex wounds.
Topics: Actin Cytoskeleton; Actins; Cell Movement; Cytoskeleton; Wound Healing
PubMed: 35074864
DOI: 10.1101/cshperspect.a041235 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018Actin is one of the most abundant intracellular proteins, essential in every eukaryotic cell type. Actin plays key roles in tissue morphogenesis, cell adhesion, muscle... (Review)
Review
Actin is one of the most abundant intracellular proteins, essential in every eukaryotic cell type. Actin plays key roles in tissue morphogenesis, cell adhesion, muscle contraction, and developmental reprogramming. Most actin studies have focused on its regulation at the protein level, either directly or through differential interactions with over a hundred intracellular binding partners. However, numerous studies emerging in recent years demonstrate specific types of nucleotide-level regulation that strongly affect non-muscle actins during cell migration and adhesion and are potentially applicable to other members of the actin family. This regulation involves zipcode-mediated actin mRNA targeting to the cell periphery, proposed to mediate local synthesis of actin at the cell leading edge, as well as the recently discovered N-terminal arginylation that specifically targets non-muscle β-actin via a nucleotide-dependent mechanism. Moreover, a study published this year suggests that actin's essential roles at the organismal level may be entirely nucleotide-dependent. This review summarizes the emerging data on actin's nucleotide-level regulation. Anat Rec, 301:1991-1998, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actins; Amino Acid Sequence; Animals; Humans; Protein Biosynthesis; Protein Processing, Post-Translational; RNA Interference
PubMed: 30312009
DOI: 10.1002/ar.23958 -
Current Opinion in Cell Biology Jun 2022Dynamic assembly and disassembly of actin proteins play a key role in the cytoskeleton, but the cellular functions of actin are not only restricted to the cytoplasmic... (Review)
Review
Dynamic assembly and disassembly of actin proteins play a key role in the cytoskeleton, but the cellular functions of actin are not only restricted to the cytoplasmic compartment. Recent studies have shown that actin spatiotemporally changes its polymerized state in the nucleus as well and such dynamic nature of actin is relevant to key nuclear events including gene expression, DNA damage response and chromatin organization. In this review, we highlight emerging roles of actin in the nuclear compartment especially in the context of embryonic development and cellular differentiation. We first explain how the actin nucleoskeleton can be formed and function in cells. Notably, nuclear actin dynamics are greatly altered when cell fates change, such as after fertilization and T cell differentiation. We discuss how the dynamic actin nucleoskeleton contributes to accomplishing developmental programs.
Topics: Actin Cytoskeleton; Actins; Cell Differentiation; Cell Nucleus; Chromatin Assembly and Disassembly; Embryonic Development; Nuclear Matrix
PubMed: 35605340
DOI: 10.1016/j.ceb.2022.102100