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Biomedicine & Pharmacotherapy =... Dec 2022Renal injury and the development of albuminuria are tightly connected with the loss of podocytes. Podocyte damages cause proteinuric renal diseases since podocyte foot... (Review)
Review
Renal injury and the development of albuminuria are tightly connected with the loss of podocytes. Podocyte damages cause proteinuric renal diseases since podocyte foot processes (FP) and their interposed slit diaphragms (SD) are the final barriers against protein loss. Podocyte effacement and the resultant deterioration of podocyte SD integrity that involve the active rearrangement of the podocyte actin cytoskeleton is a chief mechanism of proteinuric kidney diseases. The progress of these injuries can eventually lead to cell detachment and death. Due to the prominence of the actin cytoskeleton in maintaining glomerular filtration, the assessment of the molecular design and regulation of actin is a central target of podocyte research. In the current review, a comprehensive summary of the actin cytoskeleton, its constituents, and regulatory signaling pathways has been provided. Since actin-regulated cell plasticity is a crucial feature of normal podocyte function, and deteriorations in its dynamics seem to directly affect podocyte morphology and glomerular permeability, this review discusses cascades that regulate actin polymerization in podocytes.
Topics: Actins; Actin Cytoskeleton; Podocytes; Kidney Glomerulus; Intercellular Junctions
PubMed: 36411613
DOI: 10.1016/j.biopha.2022.113920 -
Science (New York, N.Y.) Sep 2022Protein synthesis generally starts with a methionine that is removed during translation. However, cytoplasmic actin defies this rule because its synthesis involves...
Protein synthesis generally starts with a methionine that is removed during translation. However, cytoplasmic actin defies this rule because its synthesis involves noncanonical excision of the acetylated methionine by an unidentified enzyme after translation. Here, we identified C19orf54, named ACTMAP (actin maturation protease), as this enzyme. Its ablation resulted in viable mice in which the cytoskeleton was composed of immature actin molecules across all tissues. However, in skeletal muscle, the lengths of sarcomeric actin filaments were shorter, muscle function was decreased, and centralized nuclei, a common hallmark of myopathies, progressively accumulated. Thus, ACTMAP encodes the missing factor required for the synthesis of mature actin and regulates specific actin-dependent traits in vivo.
Topics: Actin Cytoskeleton; Actins; Animals; Endopeptidases; Methionine; Mice; Peptide Hydrolases
PubMed: 36173861
DOI: 10.1126/science.abq5082 -
Biomolecules Feb 2023Cells use the actin cytoskeleton for many of their functions, including their division, adhesion, mechanosensing, endo- and phagocytosis, migration, and invasion. Actin... (Review)
Review
Cells use the actin cytoskeleton for many of their functions, including their division, adhesion, mechanosensing, endo- and phagocytosis, migration, and invasion. Actin bundles are the main constituent of actin-rich structures involved in these processes. An ever-increasing number of proteins that crosslink actin into bundles or regulate their morphology is being identified in cells. With recent advances in high-resolution microscopy and imaging techniques, the complex process of bundles formation and the multiple forms of physiological bundles are beginning to be better understood. Here, we review the physiochemical and biological properties of four families of highly conserved and abundant actin-bundling proteins, namely, α-actinin, fimbrin/plastin, fascin, and espin. We describe the similarities and differences between these proteins, their role in the formation of physiological actin bundles, and their properties-both related and unrelated to their bundling abilities. We also review some aspects of the general mechanism of actin bundles formation, which are known from the available information on the activity of the key actin partners involved in this process.
Topics: Actins; Actin Cytoskeleton; Actinin
PubMed: 36979385
DOI: 10.3390/biom13030450 -
Molecular Biology of the Cell Feb 2021Actin filaments and microtubules are cytoskeletal polymers that participate in many vital cell functions including division, morphogenesis, phagocytosis, and motility.... (Review)
Review
Actin filaments and microtubules are cytoskeletal polymers that participate in many vital cell functions including division, morphogenesis, phagocytosis, and motility. Despite the persistent dogma that actin filament and microtubule networks are distinct in localization, structure, and function, a growing body of evidence shows that these elements are choreographed through intricate mechanisms sensitive to either polymer. Many proteins and cellular signals that mediate actin-microtubule interactions have already been identified. However, the impact of these regulators is typically assessed with actin filament or microtubule polymers alone, independent of the other system. Further, unconventional modes and regulators coordinating actin-microtubule interactions are still being discovered. Here we examine several methods of actin-microtubule crosstalk with an emphasis on the molecular links between both polymer systems and their higher-order interactions.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Movement; Cytoskeleton; Humans; Microtubules; Morphogenesis; Signal Transduction
PubMed: 33507109
DOI: 10.1091/mbc.E19-09-0491 -
Biophysical Journal Sep 2023Adherent filopodia are elongated finger-like membrane protrusions, extending from the edges of diverse cell types and participating in cell adhesion, spreading,...
Adherent filopodia are elongated finger-like membrane protrusions, extending from the edges of diverse cell types and participating in cell adhesion, spreading, migration, and environmental sensing. The formation and elongation of filopodia are driven by the polymerization of parallel actin filaments, comprising the filopodia cytoskeletal core. Here, we report that adherent filopodia, formed during the spreading of cultured cells on galectin-8-coated substrates, tend to change the direction of their extension in a chiral fashion, acquiring a left-bent shape. Cryoelectron tomography examination indicated that turning of the filopodia tip to the left is accompanied by the displacement of the actin core bundle to the right of the filopodia midline. Reduction of the adhesion to galectin-8 by treatment with thiodigalactoside abolished this filopodia chirality. By modulating the expression of a variety of actin-associated filopodia proteins, we identified myosin-X and formin DAAM1 as major filopodia chirality promoting factors. Formin mDia1, actin filament elongation factor VASP, and actin filament cross-linker fascin were also shown to be involved. Thus, the simple actin cytoskeleton of filopodia, together with a small number of associated proteins are sufficient to drive a complex navigation process, manifested by the development of left-right asymmetry in these cellular protrusions.
Topics: Actins; Formins; Pseudopodia; Actin Cytoskeleton; Cytoskeleton
PubMed: 37301982
DOI: 10.1016/j.bpj.2023.06.003 -
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 -
Bioscience Reports Sep 2022Cell homeostasis is maintained in all organisms by the constant adjustment of cell constituents and organisation to account for environmental context. Fine-tuning of the... (Review)
Review
Cell homeostasis is maintained in all organisms by the constant adjustment of cell constituents and organisation to account for environmental context. Fine-tuning of the optimal balance of proteins for the conditions, or protein homeostasis, is critical to maintaining cell homeostasis. Actin, a major constituent of the cytoskeleton, forms many different structures which are acutely sensitive to the cell environment. Furthermore, actin structures interact with and are critically important for the function and regulation of multiple factors involved with mRNA and protein production and degradation, and protein regulation. Altogether, actin is a key, if often overlooked, regulator of protein homeostasis across eukaryotes. In this review, we highlight these roles and how they are altered following cell stress, from mRNA transcription to protein degradation.
Topics: Actin Cytoskeleton; Actins; Cytoskeleton; Homeostasis; Proteostasis; RNA, Messenger
PubMed: 36043949
DOI: 10.1042/BSR20210848 -
European Journal of Cell Biology Apr 2022Clathrin-mediated endocytosis (CME) is the major route through which cells internalise various substances and recycle membrane components. Via the coordinated action of... (Review)
Review
Clathrin-mediated endocytosis (CME) is the major route through which cells internalise various substances and recycle membrane components. Via the coordinated action of many proteins, the membrane bends and invaginates to form a vesicle that buds off-along with its contents-into the cell. The contribution of the actin cytoskeleton to this highly dynamic process in mammalian cells is not well understood. Unlike in yeast, where there is a strict requirement for actin in CME, the significance of the actin cytoskeleton to mammalian CME is variable. However, a growing number of studies have established the actin cytoskeleton as a core component of mammalian CME, and our understanding of its contribution has been increasing at a rapid pace. In this review, we summarise the state-of-the-art regarding our understanding of the endocytic cytoskeleton, its physiological significance, and the questions that remain to be answered.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Membrane; Clathrin; Cytoskeleton; Endocytosis; Mammals; Saccharomyces cerevisiae
PubMed: 35413660
DOI: 10.1016/j.ejcb.2022.151222 -
Brain Research Bulletin Mar 2023Biomolecular condensation of proteins contributes to the organization of the cytoplasm and nucleoplasm. A number of condensation processes appear to be directly involved... (Review)
Review
Biomolecular condensation of proteins contributes to the organization of the cytoplasm and nucleoplasm. A number of condensation processes appear to be directly involved in regulating the structure, function and dynamics of the cytoskeleton. Liquid-liquid phase separation of cytoskeleton proteins, together with polymerization modulators, promotes cytoskeletal fiber nucleation and branching. Furthermore, the attachment of protein condensates to the cytoskeleton can contribute to cytoskeleton stability and organization, regulate transport, create patterns of functional reaction containers, and connect the cytoskeleton with membranes. Surface-bound condensates can exert and buffer mechanical forces that give stability and flexibility to the cytoskeleton, thus, may play a large role in cell biology. In this review, we introduce the concept and role of cellular biomolecular condensation, explain its special function on cytoskeletal fiber surfaces, and point out potential definition and experimental caveats. We review the current literature on protein condensation processes related to the actin, tubulin, and intermediate filament cytoskeleton, and discuss some of them in the context of neurobiology. In summary, we provide an overview about biomolecular condensation in relation to cytoskeleton structure and function, which offers a base for the exploration and interpretation of cytoskeletal condensates in neurobiology.
Topics: Cytoskeleton; Microtubules; Cytoskeletal Proteins; Actins; Cytoplasm; Actin Cytoskeleton
PubMed: 36690162
DOI: 10.1016/j.brainresbull.2023.01.009