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International Journal of Molecular... Sep 2020Osteoclast signatures are determined by two transcriptional programs, the lineage-determining transcription pathway and the receptor activator of nuclear factor kappa-B... (Review)
Review
Osteoclast signatures are determined by two transcriptional programs, the lineage-determining transcription pathway and the receptor activator of nuclear factor kappa-B ligand (RANKL)-dependent differentiation pathways. During differentiation, mononuclear precursors become multinucleated by cell fusion. Recently, live-cell imaging has revealed a high level of heterogeneity in osteoclast multinucleation. This heterogeneity includes the difference in the differentiation states and the mobility of the fusion precursors, as well as the mode of fusion among the fusion precursors with different numbers of nuclei. In particular, fusion partners often form morphologically distinct actin-based linkages that allow two cells to exchange lipids and proteins before membrane fusion. However, the origin of this heterogeneity remains elusive. On the other hand, osteoclast multinucleation is sensitive to the environmental cues. Such cues promote the reorganization of the actin cytoskeleton, especially the formation and transformation of the podosome, an actin-rich punctate adhesion. This review covers the heterogeneity of osteoclast multinucleation at the pre-fusion stage with reference to the environment-dependent signaling pathway responsible for reorganizing the actin cytoskeleton. Furthermore, we compare osteoclast multinucleation with macrophage fusion, which results in multinucleated giant macrophages.
Topics: Actin Cytoskeleton; Animals; Cell Nucleus; Humans; Osteoclasts; Phagocytes
PubMed: 32927783
DOI: 10.3390/ijms21186629 -
Cellular and Molecular Life Sciences :... Aug 2015Actin cytoskeleton remodeling, which drives changes in cell shape and motility, is orchestrated by a coordinated control of polarized assembly of actin filaments. Signal... (Review)
Review
Actin cytoskeleton remodeling, which drives changes in cell shape and motility, is orchestrated by a coordinated control of polarized assembly of actin filaments. Signal responsive, membrane-bound protein machineries initiate and regulate polarized growth of actin filaments by mediating transient links with their barbed ends, which elongate from polymerizable actin monomers. The barbed end of an actin filament thus stands out as a hotspot of regulation of filament assembly. It is the target of both soluble and membrane-bound agonists as well as antagonists of filament assembly. Here, we review the molecular mechanisms by which various regulators of actin dynamics bind, synergize or compete at filament barbed ends. Two proteins can compete for the barbed end via a mutually exclusive binding scheme. Alternatively, two regulators acting individually at barbed ends may be bound together transiently to terminal actin subunits at barbed ends, leading to the displacement of one by the other. The kinetics of these reactions is a key in understanding how filament length and membrane-filament linkage are controlled. It is also essential for understanding how force is produced to shape membranes by mechano-sensitive, processive barbed end tracking machineries like formins and by WASP-Arp2/3 branched filament arrays. A combination of biochemical and biophysical approaches, including bulk solution assembly measurements using pyrenyl-actin fluorescence, single filament dynamics, single molecule fluorescence imaging and reconstituted self-organized filament assemblies, have provided mechanistic insight into the role of actin polymerization in motile processes.
Topics: Actin Cytoskeleton; Actin-Related Protein 2-3 Complex; Cell Movement; Cell Polarity; Microfilament Proteins; Models, Biological; Models, Molecular; Optical Imaging; Protein Binding; Protein Conformation
PubMed: 25948416
DOI: 10.1007/s00018-015-1914-2 -
FEBS Letters Apr 2013The continuous assembly and disassembly of actin filament networks is vital for cellular processes including division, growth, and motility. Network remodeling is... (Review)
Review
The continuous assembly and disassembly of actin filament networks is vital for cellular processes including division, growth, and motility. Network remodeling is facilitated by cofilins, a family of essential regulatory proteins that fragment actin filaments. Cofilin induces net structural changes in filaments that render them more compliant in bending and twisting. A model in which local stress accumulation at mechanical discontinuities, such as boundaries of bare and cofilin-decorated filament segments, accounts for the cofilin concentration dependence of severing, including maximal activity at sub-stoichiometric binding densities. Real-time imaging of cofilin-mediated filament severing supports the boundary-fracture model. The severing model predicts that fragmentation is promoted by factors modulating filament mechanics (e.g. tethering, cross-linking, or deformation), possibly explaining enhanced in vivo severing activities.
Topics: Actin Cytoskeleton; Actin Depolymerizing Factors; Actins; Animals; Biophysical Phenomena; Humans; Kinetics; Models, Molecular; Protein Binding; Thermodynamics
PubMed: 23395798
DOI: 10.1016/j.febslet.2013.01.062 -
Current Biology : CB Sep 2009Underlying the architectural complexity of plants are diverse cell types that, under the microscope, easily reveal relationships between cell structure and specialized... (Review)
Review
Underlying the architectural complexity of plants are diverse cell types that, under the microscope, easily reveal relationships between cell structure and specialized functions. Much less obvious are the mechanisms by which the cellular growth machinery and mechanical properties of the cell interact to dictate cell shape. The recent combined use of mutants, genomic analyses, sophisticated spectroscopies, and live cell imaging is providing new insight into how cytoskeletal systems and cell wall biosynthetic activities are integrated during morphogenesis. The purpose of this review is to discuss the unique geometric properties and physical processes that regulate plant cell expansion, then to overlay on this mechanical system some of the recent discoveries about the protein machines and cellular polymers that regulate cell shape. In the end, we hope to make clear that there are many interesting opportunities to develop testable mathematical models that improve our understanding of how subcellular structures, protein motors, and extracellular polymers can exert effects at spatial scales that span cells, tissues, and organs.
Topics: Actin Cytoskeleton; Biological Transport; Cell Enlargement; Cell Membrane; Cell Shape; Cell Wall; Cellulose; Cytoskeleton; Microtubules; Morphogenesis; Plant Cells; Plant Development; Plants; Pressure; Stress, Physiological
PubMed: 19906582
DOI: 10.1016/j.cub.2009.07.056 -
Biochimica Et Biophysica Acta Nov 2015Actin filament dynamics have been studied for decades in pure protein solutions or in cell extracts, but a breakthrough in the field occurred at the turn of the century... (Review)
Review
Actin filament dynamics have been studied for decades in pure protein solutions or in cell extracts, but a breakthrough in the field occurred at the turn of the century when it became possible to reconstitute networks of actin filaments, growing in a controlled but physiological manner on surfaces, mimicking the actin assembly that occurs at the plasma membrane during cell protrusion and cell shape changes. The story begins with the bacteria Listeria monocytogenes, the study of which led to the reconstitution of cellular actin polymerization on a variety of supports including plastic beads. These studies made possible the development of liposome-type substrates for filament assembly and micropatterning of actin polymerization nucleation. Based on the accumulated expertise of the last 15 years, many exciting approaches are being developed, including the addition of myosin to biomimetic actin networks to study the interplay between actin structure and contractility. The field is now poised to make artificial cells with a physiological and dynamic actin cytoskeleton, and subsequently to put these cells together to make in vitro tissues. This article is part of a Special Issue entitled: Mechanobiology.
Topics: Actin Cytoskeleton; Animals; Bacterial Proteins; Humans; Listeria monocytogenes; Membrane Proteins
PubMed: 26235437
DOI: 10.1016/j.bbamcr.2015.07.021 -
International Journal of Molecular... Mar 2019In plant cells, calcium (Ca) serves as a versatile intracellular messenger, participating in several fundamental and important biological processes. Recent studies have... (Review)
Review
In plant cells, calcium (Ca) serves as a versatile intracellular messenger, participating in several fundamental and important biological processes. Recent studies have shown that the actin cytoskeleton is not only an upstream regulator of Ca signaling, but also a downstream regulator. Ca has been shown to regulates actin dynamics and rearrangements via different mechanisms in plants, and on this basis, the upstream signaling encoded within the Ca transient can be decoded. Moreover, actin dynamics have also been proposed to act as an upstream of Ca, adjust Ca oscillations, and establish cytosolic Ca ([Ca]) gradients in plant cells. In the current review, we focus on the advances in uncovering the relationship between the actin cytoskeleton and calcium in plant cells and summarize our current understanding of this relationship.
Topics: Actin Cytoskeleton; Calcium Signaling; Plant Cells; Pollen Tube
PubMed: 30897737
DOI: 10.3390/ijms20061403 -
Developmental Cell Jun 2006Formins constitute a diverse protein family present in all eukaryotes examined. They are defined by the presence of a formin homology 2 (FH2) domain, which possesses... (Review)
Review
Formins constitute a diverse protein family present in all eukaryotes examined. They are defined by the presence of a formin homology 2 (FH2) domain, which possesses intrinsic and conserved functions regulating cytoskeletal dynamics. Over the past few years, formins have become recognized as potent nucleators of linear actin filaments that control a large variety of cellular and morphogenetic functions. Here, we review the molecular principles of formin-induced cytoskeletal rearrangements and their consequences for a growing number of biological processes.
Topics: Actin Cytoskeleton; Animals; Contractile Proteins; Humans; Microfilament Proteins; Models, Biological; Protein Binding; Protein Structure, Tertiary
PubMed: 16740473
DOI: 10.1016/j.devcel.2006.05.001 -
Proceedings of the National Academy of... Feb 2017The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid...
The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid phase of actin filaments in the presence of the physiological cross-linker, filamin. Filamin condenses short actin filaments into spindle-shaped droplets, or tactoids, with shape dynamics consistent with a continuum model of anisotropic liquids. We find that cross-linker density controls the droplet shape and deformation timescales, consistent with a variable interfacial tension and viscosity. Near the liquid-solid transition, cross-linked actin bundles show behaviors reminiscent of fluid threads, including capillary instabilities and contraction. These data reveal a liquid droplet phase of actin, demixed from the surrounding solution and dominated by interfacial tension. These results suggest a mechanism to control organization, morphology, and dynamics of the actin cytoskeleton.
Topics: Actin Cytoskeleton; Actins; Cross-Linking Reagents; Elasticity; Filamins; Kinetics; Models, Biological; Solutions; Thermodynamics; Viscosity
PubMed: 28202730
DOI: 10.1073/pnas.1616133114 -
The Journal of Cell Biology Apr 2021The turnover of actin filament networks in cells has long been considered to reflect the treadmilling behavior of pure actin filaments in vitro, where only the pointed... (Review)
Review
The turnover of actin filament networks in cells has long been considered to reflect the treadmilling behavior of pure actin filaments in vitro, where only the pointed ends depolymerize. Newly discovered molecular mechanisms challenge this notion, as they provide evidence of situations in which growing and depolymerizing barbed ends coexist.
Topics: Actin Cytoskeleton; Actins; Animals; Humans
PubMed: 33755041
DOI: 10.1083/jcb.202102020 -
Nano Letters Jan 2020Formins are one of the central players in the assembly of most actin networks in cells. The sensitivity of these processive molecular machines to mechanical tension is...
Formins are one of the central players in the assembly of most actin networks in cells. The sensitivity of these processive molecular machines to mechanical tension is now well established. However, how the activity of formins is affected by geometrical constraints related to network architecture, such as filament cross-linking and formin spatial confinement, remains largely unknown. Combining microfluidics and micropatterning, we reconstituted in vitro mDia1 formin-elongated filament bundles induced by fascin, with different geometrical constraints on the formins, and measured the impact of these constraints on formin elongation rate and processivity. When filaments are not bundled, the anchoring details of formins have only a mild impact on their processivity and do not affect their elongation rate. When formins are unanchored, we show that filament bundling by fascin reduces both their elongation rate and their processivity. Strikingly, when filaments elongated by surface-anchored formins are cross-linked together, formin elongation rate immediately decreases and processivity is reduced up to 24-fold depending on the cumulative impact of formin rotational and translational freedom. Our results reveal an unexpected crosstalk between the constraints at the filament and the formin levels. We anticipate that in cells the molecular details of formin anchoring to the plasma membrane strongly modulate formin activity at actin filament barbed ends.
Topics: Actin Cytoskeleton; Animals; Cell Membrane; Cytoskeleton; Formins; Humans
PubMed: 31797667
DOI: 10.1021/acs.nanolett.9b02241