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Molecular Microbiology Apr 2011Cells rely on extensive networks of protein fibres to help maintain their proper form and function. For species ranging from bacteria to humans, this 'cytoskeleton' is... (Review)
Review
Cells rely on extensive networks of protein fibres to help maintain their proper form and function. For species ranging from bacteria to humans, this 'cytoskeleton' is integrally involved in diverse processes including movement, DNA segregation, cell division and transport of molecular cargoes. The most abundant cytoskeletal filament-forming protein, F-actin, is remarkably well conserved across eukaryotic species. From yeast to human - an evolutionary distance of over one billion years - only about 10% of residues in actin have changed and the filament structure has been highly conserved. Surprisingly, recent structural data show this to be not the case for filamentous bacterial actins, which exhibit highly divergent helical symmetries in conjunction with structural plasticity or polymorphism, and dynamic properties that may make them uniquely suited for the specific cellular processes in which they participate. Bacterial actin filaments often organize themselves into complex structures within the prokaryotic cell, driven by molecular crowding and cation association, to form bundles (ParM) or interwoven sheets (MreB). The formation of supramolecular structures is essential for bacterial cytoskeleton function. We discuss the underlying physical principles that lead to complex structure formation and the implications these have on the physiological functions of cytoskeletal proteins.
Topics: Actin Cytoskeleton; Bacteria; Bacterial Proteins; Cytoskeleton; Genetic Variation; Macromolecular Substances
PubMed: 21362063
DOI: 10.1111/j.1365-2958.2011.07599.x -
Molecular Biology of the Cell Jan 2022IQGAP is a conserved family of actin-binding proteins with essential roles in cell motility, cytokinesis, and cell adhesion, yet there remains a limited understanding of...
IQGAP is a conserved family of actin-binding proteins with essential roles in cell motility, cytokinesis, and cell adhesion, yet there remains a limited understanding of how IQGAP proteins directly influence actin filament dynamics. To close this gap, we used single-molecule and single-filament total internal reflection fluorescence microscopy to observe IQGAP regulating actin dynamics in real time. To our knowledge, this is the first study to do so. Our results demonstrate that full-length human IQGAP1 forms dimers that stably bind to actin filament sides and transiently cap barbed ends. These interactions organize filaments into thin bundles, suppress barbed end growth, and inhibit filament disassembly. Surprisingly, each activity depends on distinct combinations of IQGAP1 domains and/or dimerization, suggesting that different mechanisms underlie each functional effect on actin. These observations have important implications for how IQGAP functions as an actin regulator in vivo and how it may be regulated in different biological settings.
Topics: Actin Cytoskeleton; Actins; Cell Adhesion; Cell Movement; Cytoskeleton; Dimerization; Humans; Microfilament Proteins; Microscopy, Fluorescence; Protein Binding; Single Molecule Imaging; ras GTPase-Activating Proteins
PubMed: 34731043
DOI: 10.1091/mbc.E21-04-0211 -
Critical Reviews in Biochemistry and... 2009The spontaneous and unregulated polymerization of actin filaments is inhibited in cells by actin monomer-binding proteins such as profilin and Tbeta4. Eukaryotic cells... (Review)
Review
The spontaneous and unregulated polymerization of actin filaments is inhibited in cells by actin monomer-binding proteins such as profilin and Tbeta4. Eukaryotic cells and certain pathogens use filament nucleators to stabilize actin polymerization nuclei, whose formation is rate-limiting. Known filament nucleators include the Arp2/3 complex and its large family of nucleation promoting factors (NPFs), formins, Spire, Cobl, VopL/VopF, TARP and Lmod. These molecules control the time and location for polymerization, and additionally influence the structures of the actin networks that they generate. Filament nucleators are generally unrelated, but with the exception of formins they all use the WASP-Homology 2 domain (WH2 or W), a small and versatile actin-binding motif, for interaction with actin. A common architecture, found in Spire, Cobl and VopL/VopF, consists of tandem W domains that bind three to four actin subunits to form a nucleus. Structural considerations suggest that NPFs-Arp2/3 complex can also be viewed as a specialized form of tandem W-based nucleator. Formins are unique in that they use the formin-homology 2 (FH2) domain for interaction with actin and promote not only nucleation, but also processive barbed end elongation. In contrast, the elongation function among W-based nucleators has been "outsourced" to a dedicated family of proteins, Eva/VASP, which are related to WASP-family NPFs.
Topics: Actin Cytoskeleton; Animals; Humans; Microfilament Proteins; Models, Biological; Protein Conformation; Protein Multimerization
PubMed: 19874150
DOI: 10.3109/10409230903277340 -
Scientific Reports Jul 2020S100A6 is a low molecular weight Ca-binding protein belonging to the S100 family. Many reports indicate that in the cell S100A6 has an influence on the organization of...
S100A6 is a low molecular weight Ca-binding protein belonging to the S100 family. Many reports indicate that in the cell S100A6 has an influence on the organization of actin filaments, but so far no direct interaction between S100A6 and actin has been shown. In the present study we investigated binding of S100A6 to actin and the actin-tropomyosin complex. The analyses were performed on G- and F-actin and two tropomyosin isoforms-Tpm1.6 and Tpm1.8. Using purified proteins and a variety of biochemical approaches we have shown that, in a Ca-bound form, S100A6 directly interacts with G- and F-actin and with tropomyosin, preferentially with isoform Tpm1.8. S100A6 and tropomyosin bind to the same population of filaments and the presence of tropomyosin on the microfilament facilitates the binding of S100A6. By applying proximity ligation assay we have found that in NIH3T3 fibroblasts S100A6 forms complexes both with actin and with tropomyosin. These results indicate that S100A6, through direct interactions with actin and tropomyosin, might regulate the organization and functional properties of microfilaments.
Topics: Actin Cytoskeleton; Actins; Animals; Mice; NIH 3T3 Cells; Protein Binding; Protein Isoforms; S100 Calcium Binding Protein A6; Tropomyosin
PubMed: 32733033
DOI: 10.1038/s41598-020-69752-y -
Open Biology Oct 2019The vast majority of cell biological studies examine function and molecular mechanisms using cells on flat surfaces: glass, plastic and more recently elastomeric... (Review)
Review
The vast majority of cell biological studies examine function and molecular mechanisms using cells on flat surfaces: glass, plastic and more recently elastomeric polymers. While these studies have provided a wealth of valuable insight, they fail to consider that most biologically occurring surfaces are curved, with a radius of curvature roughly corresponding to the length scale of cells themselves. Here, we review recent studies showing that cells detect and respond to these curvature cues by adjusting and re-orienting their cell bodies, actin fibres and nuclei as well as by changing their transcriptional programme. Modelling substratum curvature has the potential to provide fundamental new insight into cell behaviour and function .
Topics: Actin Cytoskeleton; Animals; Cell Adhesion; Cell Membrane; Cell Movement; Cellular Microenvironment; Humans; Mechanotransduction, Cellular
PubMed: 31640476
DOI: 10.1098/rsob.190155 -
Biochemical Society Transactions Feb 2023The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and... (Review)
Review
The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell to explore and navigate through its environment. It is regulated not only via a complex synergistic and competitive interplay between actin-binding proteins (ABP), but also by filament biochemistry and filament geometry. The lack of structural insights into how geometry and ABPs regulate the actin cytoskeleton limits our understanding of the molecular mechanisms that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced computational methods, it is now possible to define these molecular mechanisms involving actin and its interactors at both atomic and ultra-structural levels in vitro and in cellulo. In this review, we will provide an overview of the available cryo-EM methods, applicable to further our understanding of the actin cytoskeleton, specifically in the context of cell migration. We will discuss how these methods have been employed to elucidate ABP- and geometry-defined regulatory mechanisms in initiating, maintaining, and disassembling cellular actin networks in migratory protrusions.
Topics: Cryoelectron Microscopy; Actins; Actin Cytoskeleton; Cytoskeleton; Microfilament Proteins; Cell Movement
PubMed: 36695514
DOI: 10.1042/BST20220221 -
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 -
International Journal of Molecular... Jul 2019The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a... (Review)
Review
The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions-especially in AMD.
Topics: Actin Cytoskeleton; Aging; Animals; Biomarkers; Cytoskeleton; Extracellular Matrix; Humans; Macular Degeneration; Microtubules; Retinal Pigment Epithelium
PubMed: 31336621
DOI: 10.3390/ijms20143578 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2024There are three main classes of actin nucleation factors: Arp2/3 complexes, Spire and Formin. Spire assembles microfilaments by nucleating stable longitudinal tetramers... (Review)
Review
There are three main classes of actin nucleation factors: Arp2/3 complexes, Spire and Formin. Spire assembles microfilaments by nucleating stable longitudinal tetramers and binding actin to the growing end of the microfilament. As early as 1999, Wellington et al. identified Spire as an actin nucleating agent, however, over the years, most studies have focused on Arp2/3 and Formin proteins; there has been relatively less research on Spire as a member of the actin nucleating factors. Recent studies have shown that Spire is involved in the vesicular transport through the synthesis of actin and plays an important role in neural development. In this paper, we reviewed the structure, expression and function of Spire, and its association with disease in order to identify meaningful potential directions for studies on Spire.
Topics: Microfilament Proteins; Humans; Animals; Actins; Actin-Related Protein 2-3 Complex; Actin Cytoskeleton; Nuclear Proteins
PubMed: 38658382
DOI: No ID Found -
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