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Biochimica Et Biophysica Acta Feb 2010Formins represent a major branch of actin nucleators along with the Arp2/3 complex, Spire and Cordon-bleu. Formin-mediated actin nucleation requires the formin homology... (Review)
Review
Formins represent a major branch of actin nucleators along with the Arp2/3 complex, Spire and Cordon-bleu. Formin-mediated actin nucleation requires the formin homology 2 domain and, although the nucleation per se does not require additional factors, formin-binding proteins have been shown to be essential for the regulation of formin-dependent actin assembly in vivo. This regulation could be accomplished by formin-binding proteins being directly involved in formin-driven actin nucleation, by formin-binding proteins influencing the activated state of the formins, by linking formin-driven actin polymerization to Arp2/3 driven actin polymerization, or by influencing the subcellular localization of the formins. This review article will focus on mammalian formin-binding proteins and their roles during vital cellular processes, such as cell migration, cell division and intracellular trafficking.
Topics: Actin-Related Protein 2-3 Complex; Actins; Animals; Carrier Proteins; Cell Polarity; Fatty Acid-Binding Proteins; Fetal Proteins; Formins; Humans; Microfilament Proteins; Nuclear Proteins; Profilins; Signal Transduction; src-Family Kinases
PubMed: 19589360
DOI: 10.1016/j.bbamcr.2009.06.002 -
Molecules and Cells Apr 2010The dynamic remolding of the actin cytoskeleton is a critical part of most cellular activities, and malfunction of cytoskeletal proteins results in various human... (Review)
Review
The dynamic remolding of the actin cytoskeleton is a critical part of most cellular activities, and malfunction of cytoskeletal proteins results in various human diseases. The transition between two forms of actin, monomeric or G-actin and filamentous or F-actin, is tightly regulated in time and space by a large number of signaling, scaffolding and actin-binding proteins (ABPs). New ABPs are constantly being discovered in the post-genomic era. Most of these proteins are modular, integrating actin binding, protein-protein interaction, membrane-binding, and signaling domains. In response to extracellular signals, often mediated by Rho family GTPases, ABPs control different steps of actin cytoskeleton assembly, including filament nucleation, elongation, severing, capping, and depolymerization. This review summarizes structure-function relationships among ABPs in the regulation of actin cytoskeleton assembly.
Topics: Actins; Amino Acid Sequence; Animals; Cytoskeleton; Humans; Microfilament Proteins; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Structure, Tertiary
PubMed: 20446344
DOI: 10.1007/s10059-010-0053-8 -
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 -
Biochimica Et Biophysica Acta Apr 2001Filamins are a family of high molecular mass cytoskeletal proteins that organize filamentous actin in networks and stress fibers. Over the past few years it has become... (Comparative Study)
Comparative Study Review
Filamins are a family of high molecular mass cytoskeletal proteins that organize filamentous actin in networks and stress fibers. Over the past few years it has become clear that filamins anchor various transmembrane proteins to the actin cytoskeleton and provide a scaffold for a wide range of cytoplasmic signaling proteins. The recent cloning of three human filamins and studies on filamin orthologues from chicken and Drosophila revealed unexpected complexity of the filamin family, the biological implications of which have just started to be addressed. Expression of dysfunctional filamin-A leads to the genetic disorder of ventricular heterotopia and gives reason to expect that abnormalities in the other isogenes may also be connected with human disease. In this review aspects of filamin structure, its splice variants, binding partners and biological function will be discussed.
Topics: Actins; Amino Acid Sequence; Animals; Binding Sites; Contractile Proteins; Filamins; Humans; Membrane Proteins; Microfilament Proteins; Models, Molecular; Molecular Sequence Data; Molecular Structure; Mutation; Sequence Alignment; Signal Transduction; Species Specificity
PubMed: 11336782
DOI: 10.1016/s0167-4889(01)00072-6 -
Trends in Cell Biology Jan 2011Nebulin, a giant, actin-binding protein, is the largest member of a family of proteins (including N-RAP, nebulette, lasp-1 and lasp-2) that are assembled in a variety of... (Review)
Review
Nebulin, a giant, actin-binding protein, is the largest member of a family of proteins (including N-RAP, nebulette, lasp-1 and lasp-2) that are assembled in a variety of cytoskeletal structures, and expressed in different tissues. For decades, nebulin has been thought to act as a molecular ruler, specifying the precise length of actin filaments in skeletal muscle. However, emerging evidence suggests that nebulin should not be viewed as a ruler but as an actin filament stabilizer required for length maintenance. Nebulin has also been implicated recently in an array of regulatory functions independent of its role in actin filament length regulation. In this review, we discuss the current evolutionary, biochemical, and functional data for the nebulin family of proteins - a family whose members, both large and small, function as cytoskeletal scaffolds and stabilizers.
Topics: Actin Cytoskeleton; Animals; Evolution, Molecular; Humans; Microfilament Proteins; Muscle Proteins; Muscle, Skeletal; Myocardium
PubMed: 20951588
DOI: 10.1016/j.tcb.2010.09.005 -
Journal of Cell Science Jan 2013
Review
Topics: Actins; Animals; Humans; Microfilament Proteins; Microtubules
PubMed: 23516326
DOI: 10.1242/jcs.107250 -
Biophysical Journal Feb 2013Mathematical modeling has established its value for investigating the interplay of biochemical and mechanical mechanisms underlying actin-based motility. Because of the... (Review)
Review
Mathematical modeling has established its value for investigating the interplay of biochemical and mechanical mechanisms underlying actin-based motility. Because of the complex nature of actin dynamics and its regulation, many of these models are phenomenological or conceptual, providing a general understanding of the physics at play. But the wealth of carefully measured kinetic data on the interactions of many of the players in actin biochemistry cries out for the creation of more detailed and accurate models that could permit investigators to dissect interdependent roles of individual molecular components. Moreover, no human mind can assimilate all of the mechanisms underlying complex protein networks; so an additional benefit of a detailed kinetic model is that the numerous binding proteins, signaling mechanisms, and biochemical reactions can be computationally organized in a fully explicit, accessible, visualizable, and reusable structure. In this review, we will focus on how comprehensive and adaptable modeling allows investigators to explain experimental observations and develop testable hypotheses on the intracellular dynamics of the actin cytoskeleton.
Topics: Actin Cytoskeleton; Actins; Animals; Humans; Microfilament Proteins; Models, Biological
PubMed: 23442903
DOI: 10.1016/j.bpj.2012.12.044 -
Molecular and Cellular Biology Aug 2020Fodrin and its erythroid cell-specific isoform spectrin are actin-associated fibrous proteins that play crucial roles in the maintenance of structural integrity in... (Review)
Review
Fodrin and its erythroid cell-specific isoform spectrin are actin-associated fibrous proteins that play crucial roles in the maintenance of structural integrity in mammalian cells, which is necessary for proper cell function. Normal cell morphology is altered in diseases such as various cancers and certain neuronal disorders. Fodrin and spectrin are two-chain (αβ) molecules that are encoded by paralogous genes and share many features but also demonstrate certain differences. Fodrin (in humans, typically a heterodimer of the products of the SPTAN1 and SPTBN1 genes) is expressed in nearly all cell types and is especially abundant in neuronal tissues, whereas spectrin (in humans, a heterodimer of the products of the SPTA1 and SPTB1 genes) is expressed almost exclusively in erythrocytes. To fulfill a role in such a variety of different cell types, it was anticipated that fodrin would need to be a more versatile scaffold than spectrin. Indeed, as summarized here, domains unique to fodrin and its regulation by Ca, calmodulin, and a variety of posttranslational modifications (PTMs) endow fodrin with additional specific functions. However, how fodrin structural variations and misregulated PTMs may contribute to the etiology of various cancers and neurodegenerative diseases needs to be further investigated.
Topics: Actins; Animals; Calcium; Calmodulin; Carrier Proteins; Erythroid Cells; Humans; Microfilament Proteins; Neurons; Spectrin; Structure-Activity Relationship
PubMed: 32601107
DOI: 10.1128/MCB.00133-20 -
Trends in Cell Biology Aug 2011Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have... (Review)
Review
Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have been known for 20 years, substantial progress has been made in the past 5 years towards their understanding. In this review, we examine this progress, place it into the context of what was already known, and pose several questions that remain to be addressed. In particular, we cover the emerging consensus about the role of Type I coronins in coordinating the function of Arp2/3 complex and ADF/cofilin proteins. This coordination plays an important role in leading-edge actin dynamics and overall cell motility. Finally, we discuss the roles played by the more exotic coronins of the Type II and III classes in cellular processes away from the leading edge.
Topics: Actin Depolymerizing Factors; Actin-Related Protein 2-3 Complex; Actins; Animals; Cell Movement; Cytoskeleton; Humans; Microfilament Proteins; Protein Binding
PubMed: 21632254
DOI: 10.1016/j.tcb.2011.04.004 -
FEBS Letters Jun 2008Villin is a tissue-specific actin modifying protein that is associated with actin filaments in the microvilli and terminal web of epithelial cells. It belongs to a large... (Review)
Review
Villin is a tissue-specific actin modifying protein that is associated with actin filaments in the microvilli and terminal web of epithelial cells. It belongs to a large family of actin-binding proteins which includes actin-capping, -nucleating and/or -severing proteins such as gelsolin, severin, fragmin, adseverin/scinderin and actin crosslinking proteins such as dematin and supervillin. Studies done in epithelial cell lines and villin knock-out mice have demonstrated the function of villin in regulating actin dynamics, cell morphology, epithelial-to-mesenchymal transition, cell migration and cell survival. In addition, the ligand-binding properties of villin (F-actin, G-actin, calcium, phospholipids and phospholipase C-gamma1) are mechanistically important for the crosstalk between signaling pathways and actin reorganization in epithelial cells.
Topics: Actins; Animals; Apoptosis; Apoptosis Regulatory Proteins; Cell Movement; Cell Survival; Epithelial Cells; Humans; Mice; Mice, Knockout; Microfilament Proteins; Protein Structure, Tertiary
PubMed: 18307996
DOI: 10.1016/j.febslet.2008.02.040