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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 -
Cell Jun 2024Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell...
Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the bent-closed integrin conformation, which predominates on cell surfaces, is followed within milliseconds by two concerted changes, leg extension and headpiece opening, to give the high-affinity integrin conformation. The extended-closed integrin conformation is not an intermediate but can be directly accessed from the extended-open conformation and provides a pathway for ligand dissociation. In contrast to ligand, talin, which links the integrin β-subunit cytoplasmic domain to the actin cytoskeleton, modestly stabilizes but does not induce extension or opening. Integrin activation is thus initiated by outside-in signaling and followed by inside-out signaling. Our results further imply that talin binding is insufficient for inside-out integrin activation and that tensile force transmission through the ligand-integrin-talin-actin cytoskeleton complex is required.
Topics: Animals; Humans; Mice; Actin Cytoskeleton; Cell Adhesion; CHO Cells; Cricetulus; Integrins; Ligands; Protein Binding; Protein Conformation; Signal Transduction; Single Molecule Imaging; Talin
PubMed: 38772370
DOI: 10.1016/j.cell.2024.04.049 -
Gene Jun 2021Filamin A(FLNa) is an actin-binding protein, which participates in the formation of the cytoskeleton, anchors a variety of proteins in the cytoskeleton and regulates... (Review)
Review
Filamin A(FLNa) is an actin-binding protein, which participates in the formation of the cytoskeleton, anchors a variety of proteins in the cytoskeleton and regulates cell adhesion and migration. It is involved in signal transduction, cell proliferation and differentiation, pseudopodia formation, vesicle transport, tumor resistance and genetic diseases by binding with interacting proteins. In order to fully elucidate the structure, function and pathogenesis of FLNa, we summarized all substances which directly or indirectly act on FLNa so far, upstream and downstream targets which having effect on it, signaling pathways and their functions. It also recorded the expression and effect of FLNa in different diseases, including hereditary disease and tumors.
Topics: Actin Cytoskeleton; Cell Adhesion; Cell Movement; Drug Resistance, Neoplasm; Filamins; Genetic Predisposition to Disease; Humans; Neoplasms
PubMed: 33737122
DOI: 10.1016/j.gene.2021.145575 -
Current Opinion in Cell Biology Apr 2024The cytoskeleton, comprising actin microfilaments, microtubules, and intermediate filaments, is crucial for cell motility and tissue integrity. While prior studies... (Review)
Review
The cytoskeleton, comprising actin microfilaments, microtubules, and intermediate filaments, is crucial for cell motility and tissue integrity. While prior studies largely focused on individual cytoskeletal networks, recent research underscores the interconnected nature of these systems in fundamental cellular functions like adhesion, migration, and division. Understanding the coordination of these distinct networks in both time and space is essential. This review synthesizes current findings on the intricate interplay between these networks, emphasizing the pivotal role of intermediate filaments. Notably, these filaments engage in extensive crosstalk with microfilaments and microtubules through direct molecular interactions, cytoskeletal linkers, and molecular motors that form molecular bridges, as well as via more complex regulation of intracellular signaling.
Topics: Intermediate Filaments; Cytoskeleton; Microtubules; Actin Cytoskeleton; Cell Movement; Actins
PubMed: 38359728
DOI: 10.1016/j.ceb.2024.102325 -
Nature Methods Feb 2023
Topics: Actins; Actin Cytoskeleton
PubMed: 36765135
DOI: 10.1038/s41592-022-01762-2 -
Methods in Molecular Biology (Clifton,... 2021Mechanical forces have emerged as essential regulators of cell organization, proliferation, migration, and polarity to regulate cellular and tissue homeostasis. Changes... (Review)
Review
Mechanical forces have emerged as essential regulators of cell organization, proliferation, migration, and polarity to regulate cellular and tissue homeostasis. Changes in forces or loss of the cellular response to them can result in abnormal embryonic development and diseases. Over the past two decades, many efforts have been put in deciphering the molecular mechanisms that convert forces into biochemical signals, allowing for the identification of many mechanotransducer proteins. Here we discuss how PDZ proteins are emerging as new mechanotransducer proteins by altering their conformations or localizations upon force loads, leading to the formation of macromolecular modules tethering the cell membrane to the actin cytoskeleton.
Topics: Actin Cytoskeleton; Animals; Cell Membrane; Humans; Mechanotransduction, Cellular; Multiprotein Complexes; PDZ Domains; Proteins
PubMed: 34014527
DOI: 10.1007/978-1-0716-1166-1_15 -
European Journal of Cell Biology Jun 2024At the cell surface, the actin cytoskeleton and the plasma membrane interact reciprocally in a variety of processes related to the remodeling of the cell surface. The... (Review)
Review
At the cell surface, the actin cytoskeleton and the plasma membrane interact reciprocally in a variety of processes related to the remodeling of the cell surface. The actin cytoskeleton has been known to modulate membrane organization and reshape the membrane. To this end, actin-membrane linking molecules play a major role in regulating actin assembly and spatially direct the interaction between the actin cytoskeleton and the membrane. While studies in cells have provided a wealth of knowledge on the molecular composition and interactions of the actin-membrane interface, the complex molecular interactions make it challenging to elucidate the precise actions of the actin-membrane linkers at the interface. Synthetic reconstituted systems, consisting of model membranes and purified proteins, have been a powerful approach to elucidate how actin-membrane linkers direct actin assembly to drive membrane shape changes. In this review, we will focus only on several actin-membrane linkers that have been studied by using reconstitution systems. We will discuss the design principles of these reconstitution systems and how they have contributed to the understanding of the cellular functions of actin-membrane linkers. Finally, we will provide a perspective on future research directions in understanding the intricate actin-membrane interaction.
Topics: Cell Membrane; Actins; Humans; Animals; Actin Cytoskeleton
PubMed: 38461706
DOI: 10.1016/j.ejcb.2024.151402 -
Frontiers in Immunology 2020A growing number of monogenic immune-mediated diseases have been related to genes involved in pathways of actin cytoskeleton remodeling. Increasing evidences associate... (Review)
Review
A growing number of monogenic immune-mediated diseases have been related to genes involved in pathways of actin cytoskeleton remodeling. Increasing evidences associate cytoskeleton defects to autoinflammatory diseases and primary immunodeficiencies. We reviewed the pathways of actin cytoskeleton remodeling in order to identify inflammatory and immunological manifestations associated to pathological variants. We list more than twenty monogenic diseases, ranging from pure autoinflammatory conditions as familial Mediterranean fever, mevalonate kinase deficiency and PAPA syndrome, to classic and novel primary immunodeficiencies as Wiskott-Aldrich syndrome and DOCK8 deficiency, characterized by the presence of concomitant inflammatory and autoimmune manifestations, such as vasculitis and cytopenia, to severe and recurrent infections. We classify these disorders according to the role of the mutant gene in actin cytoskeleton remodeling, and in particular as disorders of transcription, elongation, branching and activation of actin. This expanding field of rare immune disorders offers a new perspective to all immunologists to better understand the physiological and pathological role of actin cytoskeleton in cells of innate and adaptive immunity.
Topics: Actin Cytoskeleton; Animals; Autoimmunity; Genetic Predisposition to Disease; Humans; Immunologic Deficiency Syndromes; Inflammation; Mutation; Phenotype; Signal Transduction
PubMed: 33488606
DOI: 10.3389/fimmu.2020.604206 -
Development (Cambridge, England) Sep 2020Actomyosin networks are some of the most crucial force-generating components present in developing tissues. The contractile forces generated by these networks are... (Review)
Review
Actomyosin networks are some of the most crucial force-generating components present in developing tissues. The contractile forces generated by these networks are harnessed during morphogenesis to drive various cell and tissue reshaping events. Recent studies of these processes have advanced rapidly, providing us with insights into how these networks are initiated, positioned and regulated, and how they act via individual contractile pulses and/or the formation of supracellular cables. Here, we review these studies and discuss the mechanisms that underlie the construction and turnover of such networks and structures. Furthermore, we provide an overview of how ratcheted processivity emerges from pulsed events, and how tissue-level mechanics are the coordinated output of many individual cellular behaviors.
Topics: Actin Cytoskeleton; Actomyosin; Animals; Epithelium; Humans; Morphogenesis
PubMed: 32878903
DOI: 10.1242/dev.186502 -
Advances in Biological Regulation Jan 2021A major question in cell biology is, how are organelles and large macromolecular complexes transported within a cell? Myosin V molecular motors play critical roles in... (Review)
Review
A major question in cell biology is, how are organelles and large macromolecular complexes transported within a cell? Myosin V molecular motors play critical roles in the distribution of organelles, vesicles, and mRNA. Mis-localization of organelles that depend on myosin V motors underlie diseases in the skin, gut, and brain. Thus, the delivery of organelles to their proper destination is important for animal physiology and cellular function. Cargoes attach to myosin V motors via cargo specific adaptor proteins, which transiently bridge motors to their cargoes. Regulation of these adaptor proteins play key roles in the regulation of cargo transport. Emerging studies reveal that cargo adaptors play additional essential roles in the activation of myosin V, and the regulation of actin filaments. Here, we review how motor-adaptor interactions are controlled to regulate the proper loading and unloading of cargoes, as well as roles of adaptor proteins in the regulation of myosin V activity and the dynamics of actin filaments.
Topics: Actin Cytoskeleton; Animals; Humans; Myosin Type V; Organelles; Protein Binding; Protein Transport
PubMed: 33541831
DOI: 10.1016/j.jbior.2021.100787