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Current Biology : CB May 2021Actin is one of the most abundant proteins in eukaryotes. Discovered in muscle and described as far back as 1887, actin was first purified in 1942. It plays myriad roles...
Actin is one of the most abundant proteins in eukaryotes. Discovered in muscle and described as far back as 1887, actin was first purified in 1942. It plays myriad roles in essentially every eukaryotic cell. Actin is central to development, muscle contraction, and cell motility, and it also functions in the nucleus, to name a spectrum of examples. The flexibility of actin function stems from two factors: firstly, it is dynamic, transitioning between monomer and filament, and, secondly, there are hundreds of actin-binding proteins that build and organize specific actin-based structures. Of prime importance are actin nucleators - proteins that stimulate de novo formation of actin filaments. There are three known classes of actin nucleators: the Arp2/3 complex, formins, and tandem WASP homology 2 (WH2) nucleators. Each class nucleates by a distinct mechanism that contributes to the organization of the larger structure being built. Evidence shows that the Arp2/3 complex produces branched actin filaments, remaining bound at the branch point, while formins create linear actin filaments, remaining bound at the growing end. Here, we focus on the formin family of actin nucleators.
Topics: Actin Cytoskeleton; Actin-Related Protein 2-3 Complex; Actins; Formins; Microfilament Proteins
PubMed: 34033783
DOI: 10.1016/j.cub.2021.02.047 -
Current Biology : CB May 2021Arit Ghosh and Velia Fowler introduce the structural features and functions of tropomodulins - actin-binding proteins that cap the slow-growing (pointed) ends of actin...
Arit Ghosh and Velia Fowler introduce the structural features and functions of tropomodulins - actin-binding proteins that cap the slow-growing (pointed) ends of actin filaments.
Topics: Actin Cytoskeleton; Actins; Microfilament Proteins; Tropomodulin
PubMed: 34033779
DOI: 10.1016/j.cub.2021.01.055 -
Histochemistry and Cell Biology Apr 2016Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research.... (Review)
Review
Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research. One of these new aspects is the discovery of the existence of nuclear actin which became evident only recently. Nuclear activities including transcriptional activation in the case of all three RNA polymerases, editing and nuclear export of mRNAs, and chromatin remodeling all depend on actin. It also became clear that there is a fine-tuned equilibrium between cytoplasmic and nuclear actin pools and that this balance is ensured by an export-import system dedicated to actin. After over half a century of research on conventional actin and its organizing partners in the cytoplasm, it was also an unexpected finding that the nucleus contains more than 30 actin-binding proteins and new classes of actin-related proteins which are not able to form filaments but had evolved nuclear-specific functions. The actin-binding and actin-related proteins in the nucleus have been linked to RNA transcription and processing, nuclear transport, and chromatin remodeling. In this paper, we attempt to provide an overview of the wide range of information that is now available about actin, actin-binding, and actin-related proteins in the nucleus.
Topics: Actins; Animals; Cell Nucleolus; Humans; Microfilament Proteins
PubMed: 26847179
DOI: 10.1007/s00418-015-1400-9 -
Nucleus (Austin, Tex.) 2013Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many... (Review)
Review
Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. Among these proteins several studies have identified classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton. These discoveries have raised the possibility that nuclear actin performs its multi task activities through tight interactions with different sets of proteins. This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states. Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity. By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified.
Topics: Actins; Animals; Cell Nucleus; Microfilament Proteins; Protein Interaction Maps; RNA Polymerase II; Transcription Elongation, Genetic; Transcriptional Activation
PubMed: 23138849
DOI: 10.4161/nucl.22798 -
Annual Review of Biophysics 2012Filamins are essential, evolutionarily conserved, modular, multidomain, actin-binding proteins that organize the actin cytoskeleton and maintain extracellular matrix... (Review)
Review
Filamins are essential, evolutionarily conserved, modular, multidomain, actin-binding proteins that organize the actin cytoskeleton and maintain extracellular matrix connections by anchoring actin filaments to transmembrane receptors. By cross-linking and anchoring actin filaments, filamins stabilize the plasma membrane, provide cellular cortical rigidity, and contribute to the mechanical stability of the plasma membrane and the cell cortex. In addition to binding actin, filamins interact with more than 90 other binding partners including intracellular signaling molecules, receptors, ion channels, transcription factors, and cytoskeletal and adhesion proteins. Thus, filamins scaffold a wide range of signaling pathways and are implicated in the regulation of a diverse array of cellular functions including motility, maintenance of cell shape, and differentiation. Here, we review emerging structural and functional evidence that filamins are mechanosensors and/or mechanotransducers playing essential roles in helping cells detect and respond to physical forces in their local environment.
Topics: Animals; Cell Membrane; Cell Movement; Cell Shape; Contractile Proteins; Cytoskeleton; Filamins; Humans; Mechanotransduction, Cellular; Microfilament Proteins; Protein Binding; Protein Structure, Tertiary; Signal Transduction
PubMed: 22404683
DOI: 10.1146/annurev-biophys-050511-102252 -
Biochimica Et Biophysica Acta Feb 2010Formins have recently been recognized as prominent regulators of the microtubule (MT) cytoskeleton where they modulate the dynamics of selected MTs in interphase and... (Review)
Review
Formins have recently been recognized as prominent regulators of the microtubule (MT) cytoskeleton where they modulate the dynamics of selected MTs in interphase and mitosis. The association of formins with the MT cytoskeleton and their action on MT dynamics are relatively unexplored areas, yet growing evidence supports a direct role in their regulation of MT stability independent of their activity on actin. Formins regulate MT stability alone or in combination with accessory MT binding proteins that have previously been implicated in the stabilization of MTs downstream of polarity cues. As actin and MT arrays are typically remodeled downstream of signaling pathways that orchestrate cell shape and division, formins are emerging as excellent candidates for coordinating the responses of the cytoskeletal in diverse regulated and homeostatic processes.
Topics: Animals; Cell Division; Cytoskeleton; Fetal Proteins; Formins; Microfilament Proteins; Microtubules; Neurons; Nuclear Proteins; Viruses
PubMed: 19631698
DOI: 10.1016/j.bbamcr.2009.07.006 -
Biochemical Society Transactions Feb 2015Understanding how actin filaments are nucleated, polymerized and disassembled in close proximity to cell membranes is an area of growing interest. Protrusion of the... (Review)
Review
Understanding how actin filaments are nucleated, polymerized and disassembled in close proximity to cell membranes is an area of growing interest. Protrusion of the plasma membrane is required for cell motility, whereas inward curvature or invagination is required for endocytic events. These morphological changes in membrane are often associated with rearrangements of actin, but how the many actin-binding proteins of eukaryotes function in a co-ordinated way to generate the required responses is still not well understood. Identification and analysis of proteins that function at the interface between the plasma membrane and actin-regulatory networks is central to increasing our knowledge of the mechanisms required to transduce the force of actin polymerization to changes in membrane morphology. The Ysc84/SH3yl1 proteins have not been extensively studied, but work in both yeast and mammalian cells indicate that these proteins function at the hub of networks integrating regulation of filamentous actin (F-actin) with changes in membrane morphology.
Topics: Amino Acid Sequence; Animals; Binding Sites; Carrier Proteins; Conserved Sequence; Humans; Membrane Proteins; Microfilament Proteins; Molecular Sequence Data; Protein Binding; Protein Interaction Maps; Saccharomyces cerevisiae Proteins
PubMed: 25619255
DOI: 10.1042/BST20140221 -
BMB Reports Jan 2016Spectraplakins are crucially important communicators, linking cytoskeletal components to each other and cellular junctions. Microtubule actin crosslinking factor 1... (Review)
Review
Spectraplakins are crucially important communicators, linking cytoskeletal components to each other and cellular junctions. Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking family 7 (ACF7), is a member of the spectraplakin family. It is expressed in numerous tissues and cells as one extensively studied spectraplakin. MACF1 has several isoforms with unique structures and well-known function to be able to crosslink F-actin and microtubules. MACF1 is one versatile spectraplakin with various functions in cell processes, embryo development, tissue-specific functions, and human diseases. The importance of MACF1 has become more apparent in recent years. Here, we summarize the current knowledge on the presence and function of MACF1 and provide perspectives on future research of MACF1 based on our studies and others.
Topics: Actins; Animals; Cell Movement; Embryo, Mammalian; Humans; Microfilament Proteins; Protein Binding; Protein Isoforms; Protein Structure, Tertiary; Signal Transduction
PubMed: 26521939
DOI: 10.5483/BMBRep.2016.49.1.185 -
PLoS Biology Nov 2020Lifeact is a short actin-binding peptide that is used to visualize filamentous actin (F-actin) structures in live eukaryotic cells using fluorescence microscopy....
Lifeact is a short actin-binding peptide that is used to visualize filamentous actin (F-actin) structures in live eukaryotic cells using fluorescence microscopy. However, this popular probe has been shown to alter cellular morphology by affecting the structure of the cytoskeleton. The molecular basis for such artefacts is poorly understood. Here, we determined the high-resolution structure of the Lifeact-F-actin complex using electron cryo-microscopy (cryo-EM). The structure reveals that Lifeact interacts with a hydrophobic binding pocket on F-actin and stretches over 2 adjacent actin subunits, stabilizing the DNase I-binding loop (D-loop) of actin in the closed conformation. Interestingly, the hydrophobic binding site is also used by actin-binding proteins, such as cofilin and myosin and actin-binding toxins, such as the hypervariable region of TccC3 (TccC3HVR) from Photorhabdus luminescens and ExoY from Pseudomonas aeruginosa. In vitro binding assays and activity measurements demonstrate that Lifeact indeed competes with these proteins, providing an explanation for the altering effects of Lifeact on cell morphology in vivo. Finally, we demonstrate that the affinity of Lifeact to F-actin can be increased by introducing mutations into the peptide, laying the foundation for designing improved actin probes for live cell imaging.
Topics: Actins; Animals; Bacterial Toxins; Binding Sites; Binding, Competitive; Cofilin 1; Cryoelectron Microscopy; Fluorescent Dyes; HEK293 Cells; Humans; Hydrophobic and Hydrophilic Interactions; In Vitro Techniques; Microfilament Proteins; Microscopy, Confocal; Models, Molecular; Myosins; Peptide Fragments; Protein Engineering; Protein Interaction Domains and Motifs; Rabbits; Recombinant Fusion Proteins; Saccharomyces cerevisiae Proteins
PubMed: 33216759
DOI: 10.1371/journal.pbio.3000925 -
Nature Structural & Molecular Biology Apr 2014Autophagy complements the ubiquitin-proteasome system in mediating protein turnover. Whereas the proteasome degrades individual proteins modified with ubiquitin chains,... (Review)
Review
Autophagy complements the ubiquitin-proteasome system in mediating protein turnover. Whereas the proteasome degrades individual proteins modified with ubiquitin chains, autophagy degrades many proteins and organelles en masse. Macromolecules destined for autophagic degradation are 'selected' through sequestration within a specialized double-membrane compartment termed the phagophore, the precursor to an autophagosome, and then are hydrolyzed in a lysosome- or vacuole-dependent manner. Notably, a pair of distinctive ubiquitin-like proteins (UBLs), Atg8 and Atg12, regulate degradation by autophagy in unique ways by controlling autophagosome biogenesis and recruitment of specific cargos during selective autophagy. Here we review structural mechanisms underlying the functions and conjugation of these UBLs that are specialized to provide interaction platforms linked to phagophore membranes.
Topics: Adaptor Proteins, Signal Transducing; Autophagy; Autophagy-Related Protein 8 Family; Autophagy-Related Proteins; Cysteine Endopeptidases; Humans; Microfilament Proteins; Models, Biological; Proteasome Endopeptidase Complex; Proteolysis; Ubiquitins
PubMed: 24699082
DOI: 10.1038/nsmb.2787