The Experts below are selected from a list of 2394 Experts worldwide ranked by ideXlab platform
James R Bamburg - One of the best experts on this subject based on the ideXlab platform.
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redundant and non redundant functions of Actin Depolymerizing Factor adf and cofilin in metastasis review
2011Co-Authors: Lubna H Tahtamouni, James R BamburgAbstract:Tumor cell motility is the hallmark of invasion and an essential step in metastasis. Cellular changes that occur during the progression of cancer affect proteins that drive Actin dynamics; these changes modulate cell cycle progression and lead to more invasive cancers. Actin Depolymerizing Factor (ADF)/cofilins (Actin dynamizing proteins) and their regulatory proteins are involved in the initiation of early steps in cell motility. ADF/cofilins play important roles in various stages of cancer progression including cell polarization and polarized migration, escape from apoptosis, and secretion of metalloproteases, all of which are important in metastasis. Vertebrates express ADF, cofilin-1 and cofilin-2, and even though ADF and cofilin have many qualitatively similar biochemical properties, they differ quantitatively in Actin interaction and in some types of regulation and, thus, are not functionally identical. This review compares the activities of these two proteins with respect to how they may function during tumor cell invasion. Understanding the molecular pathways of tumor invasion will provide new diagnostic approaches and targets for the treatment of metastatic cancer. ﺮﺒﺘﻌﺗ
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proteins of the Actin Depolymerizing Factor cofilin family
2007Co-Authors: Janel D Funk, James R BamburgAbstract:Actin Depolymerizing Factor (ADF) and cofilin are the founding members of a group of structurally and functionally related Actin binding proteins now collectively known as the ADF/cofilin (AC) family. AC proteins are expressed in all eukaryotic organisms, and their unique ability to bind and dynamize filamentous Actin renders them essential to all cellular processes dependent upon Actin dynamics. Cell division, cell motility and neuronal pathfinding, membrane dynamics, and cell polarization could not proceed without the aid of these remarkable proteins.
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Proteins of the Actin Depolymerizing Factor/Cofilin Family
Actin-Monomer-Binding Proteins, 2007Co-Authors: Janel D Funk, James R BamburgAbstract:Actin Depolymerizing Factor (ADF) and cofilin are the founding members of a group of structurally and functionally related Actin binding proteins now collectively known as the ADF/cofilin (AC) family. AC proteins are expressed in all eukaryotic organisms, and their unique ability to bind and dynamize filamentous Actin renders them essential to all cellular processes dependent upon Actin dynamics. Cell division, cell motility and neuronal pathfinding, membrane dynamics, and cell polarization could not proceed without the aid of these remarkable proteins.
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Regulating filopodial dynamics through Actin-Depolymerizing Factor/cofilin
Anatomical Science International, 2004Co-Authors: Joseph Fass, Scott Gehler, Patrick Sarmiere, Paul Letourneau, James R BamburgAbstract:The regulation of filopodial dynamics by neurotrophins and other guidance cues plays an integral role in growth cone pathfinding. Filopodia are F-Actin-based structures that explore the local environment, generate forces and play a role in growth cone translocation. Here, we review recent research showing that the Actin-Depolymerizing Factor (ADF)/cofilin family of proteins mediates changes in the length and number of growth cone filopodia in response to brain-derived neurotrophic Factor (BDNF). Although inhibition of myosin contractility also causes filopodial elongation, the elongation in response to BDNF does not occur through a myosin-dependent pathway. Active ADF/cofilin increases the rate of cycling between the monomer and polymer pools and is critical for the BDNF-induced changes. Thus, we discuss potential mechanisms by which ADF/cofilin may affect filopodial initiation and length change via its effects on F-Actin dynamics in light of past research on Actin and myosin function in growth cones.
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regulating filopodial dynamics through Actin Depolymerizing Factor cofilin
Anatomical Science International, 2004Co-Authors: Joseph Fass, Scott Gehler, Patrick Sarmiere, Paul Letourneau, James R BamburgAbstract:The regulation of filopodial dynamics by neurotrophins and other guidance cues plays an integral role in growth cone pathfinding. Filopodia are F-Actin-based structures that explore the local environment, generate forces and play a role in growth cone translocation. Here, we review recent research showing that the Actin-Depolymerizing Factor (ADF)/cofilin family of proteins mediates changes in the length and number of growth cone filopodia in response to brain-derived neurotrophic Factor (BDNF). Although inhibition of myosin contractility also causes filopodial elongation, the elongation in response to BDNF does not occur through a myosin-dependent pathway. Active ADF/cofilin increases the rate of cycling between the monomer and polymer pools and is critical for the BDNF-induced changes. Thus, we discuss potential mechanisms by which ADF/cofilin may affect filopodial initiation and length change via its effects on F-Actin dynamics in light of past research on Actin and myosin function in growth cones.
Christopher J Staiger - One of the best experts on this subject based on the ideXlab platform.
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arabidopsis Actin Depolymerizing Factor atadf4 mediates defense signal transduction triggered by the pseudomonas syringae effector avrpphb
Plant Physiology, 2009Co-Authors: Miaoying Tian, Faisal Chaudhry, R Ichard B. Meagher, Daniel R Ruzicka, Christopher J StaigerAbstract:The Actin cytoskeleton has been implicated in plant defenses against pathogenic fungi and oomycetes with limited, indirect evidence. To date, there are no reports linking Actin with resistance against phytopathogenic bacteria. The dynamic behavior of Actin filaments is regulated by a diverse array of Actin-binding proteins, among which is the Actin-Depolymerizing Factor (ADF) family of proteins. Here, we demonstrate that Actin dynamics play a role in the activation of gene-for-gene resistance in Arabidopsis (Arabidopsis thaliana) following inoculation with the phytopathogenic bacterium Pseudomonas syringae pv tomato. Using a reverse genetics approach, we explored the roles of Arabidopsis ADFs in plant defenses. AtADF4 was identified as being specifically required for resistance triggered by the effector AvrPphB but not AvrRpt2 or AvrB. Recombinant AtADF4 bound to monomeric Actin (G-Actin) with a marked preference for the ADP-loaded form and inhibited the rate of nucleotide exchange on G-Actin, indicating that AtADF4 is a bona fide Actin-Depolymerizing Factor. Exogenous application of the Actin-disrupting agent cytochalasin D partially rescued the Atadf4 mutant in the AvrPphB-mediated hypersensitive response, demonstrating that AtADF4 mediates defense signaling through modification of the Actin cytoskeleton. Unlike the mechanism by which the Actin cytoskeleton confers resistance against fungi and oomycetes, AtADF4 is not involved in resistance against pathogen entry. Collectively, this study identifies AtADF4 as a novel component of the plant defense signaling pathway and provides strong evidence for Actin dynamics as a primary component that orchestrates plant defenses against P. syringae.
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Arabidopsis Actin-Depolymerizing Factor AtADF4 Mediates Defense Signal Transduction Triggered by
2009Co-Authors: Miaoying Tian, Faisal Chaudhry, R. Ruzicka, R Ichard B. Meagher, Christopher J StaigerAbstract:The Actin cytoskeleton has been implicated in plant defenses against pathogenic fungi and oomycetes with limited, indirect evidence. To date, there are no reports linking Actin with resistance against phytopathogenic bacteria. The dynamic behavior of Actin filaments is regulated by a diverse array of Actin-binding proteins, among which is the Actin-Depolymerizing Factor (ADF) family of proteins. Here, we demonstrate that Actin dynamics play a role in the activation of gene-for-gene resistance in Arabidopsis (Arabidopsis thaliana) following inoculation with the phytopathogenic bacterium Pseudomonas syringae pv tomato. Using a reverse genetics approach, we explored the roles of Arabidopsis ADFs in plant defenses. AtADF4 was identified as being specifically required for resistance triggered by the effector AvrPphB but not AvrRpt2 or AvrB. Recombinant AtADF4 bound to monomeric Actin (G-Actin) with a marked preference for the ADP-loaded form and inhibited the rate of nucleotide exchange on G-Actin, indicating that AtADF4 is a bona fide Actin-Depolymerizing Factor. Exogenous application of the Actindisrupting agent cytochalasin D partially rescued the Atadf4 mutant in the AvrPphB-mediated hypersensitive response, demonstrating that AtADF4 mediates defense signaling through modification of the Actin cytoskeleton. Unlike the mechanism by which the Actin cytoskeleton confers resistance against fungi and oomycetes, AtADF4 is not involved in resistance against pathogen entry. Collectively, this study identifies AtADF4 as a novel component of the plant defense signaling pathway and provides strong evidence for Actin dynamics as a primary component that orchestrates plant defenses against P. syringae.
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Actin Depolymerizing Factor
2000Co-Authors: David R Kovar, Christopher J StaigerAbstract:Unlike other Actin-binding proteins, Actin Depolymerizing Factor (ADF) binds to both filamentous and globular Actin, and causes the rapid depolymerization of Actin filaments. ADF localizes to sites of active Actin dynamics, including growing maize root hairs. ADF activity is regulated by a variety of stimuli implicated in affecting Actin organization, such as pH changes, phosphorylation and polyphosphoinositides. Our current understanding of ADF’s role in regulating Actin dynamics has been greatly enhanced through examination of the biochemical properties of plant ADFs. ADF depolymerizes Actin filaments by a combination of severing activity and enhancing the rate of Actin monomer dissociation from the pointed end. As a result, ADF-induced depolymerization creates a large pool of Actin subunits. When the ends of Actin filaments are uncapped, this pool is able to rapidly repolymerize. However, when filament ends are capped, repolymerization can not occur. Therefore, depending upon the presence of Actin-filament capping Factors, ADF either drives filament turnover or induces total depolymerization.
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profilin and Actin Depolymerizing Factor modulators of Actin organization in plants
Trends in Plant Science, 1997Co-Authors: Christopher J Staiger, David R Kovar, Bryan C Gibbon, Laura E ZoniaAbstract:A striking feature of the eukaryotic Actin cytoskeleton is its ability to undergo dramatic reorganization in response to internal and environmental stimuli. In plant cells, several cellular processes depend on, or are coincident with, reorganization of the Actin cytoskeleton, including division, differentiation, light-induced plastid migration, wound repair and response to pathogen attack. Understanding how the Actin cytoskeleton responds to these internal and extracellular Factors requires a detailed understanding of the molecular mechanisms that coordinate Actin polymerization and depolymerization. There is increasing evidence that the small Actin-binding proteins profilin and Actin-Depolymerizing Factor regulate Actin dynamics in plant cells. These proteins may serve to integrate signaling cues and translate this information to remodel the cytoplasmic architecture.
Kurato Mohri - One of the best experts on this subject based on the ideXlab platform.
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the two caenorhabditis elegans Actin Depolymerizing Factor cofilin proteins differently enhance Actin filament severing and depolymerization
Biochemistry, 2005Co-Authors: Sawako Yamashiro, Kurato MohriAbstract:Actin-Depolymerizing Factor (ADF)/cofilin enhances the turnover of Actin filaments by two separable activities: filament severing and pointed-end depolymerization. Multicellular organisms express multiple ADF/cofilin isoforms in a tissue-specific manner, and the vertebrate proteins are grouped into ADFs and cofilins on the basis of their biochemical activity. A recent comparative study has shown that ADF has greater severing and Depolymerizing activities than cofilin [Chen, H., Bernstein, B. W., Sneider, J. M., Boyle, J. A., Minamide, L. S., and Bamburg, J. R. (2004) Biochemistry 43, 7127-7142]. Here, we show that the two Caenorhabditis elegans ADF/cofilin isoforms exhibit different activities for severing and Depolymerizing Actin filaments. The ADF-like non-muscle isoform UNC-60A had greater activities to cause net depolymerization and inhibit polymerization than the cofilin-like muscle isoform UNC-60B. Surprisingly, UNC-60B exhibited much stronger severing activity than UNC-60A, which was the opposite of what was observed for vertebrate counterparts. Moreover, UNC-60B induced much faster pointed-end depolymerization of rabbit muscle Actin than UNC-60A, while UNC-60A caused slightly faster depolymerization of C. elegans Actin than UNC-60B. These results suggest that cofilin-like UNC-60B is kinetically more efficient in enhancing Actin turnover than ADF-like UNC-60A, while ADF-like UNC-60A is suitable for maintaining higher concentrations of monomeric Actin. These functional differences might be specifically adapted for different Actin dynamics in muscle and non-muscle cells.
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identification of functional residues on caenorhabditis elegans Actin interActing protein 1 unc 78 for disassembly of Actin Depolymerizing Factor cofilin bound Actin filaments
Journal of Biological Chemistry, 2004Co-Authors: Kurato Mohri, S Vorobiev, A A Fedorov, S C AlmoAbstract:Abstract Actin-interActing protein 1 (AIP1) is a WD40 repeat protein that enhances Actin filament disassembly in the presence of Actin-Depolymerizing Factor (ADF)/cofilin. AIP1 also caps the barbed end of ADF/cofilin-bound Actin filament. However, the mechanism by which AIP1 interacts with ADF/cofilin and Actin is not clearly understood. We determined the crystal structure of Caenorhabditis elegans AIP1 (UNC-78), which revealed 14 WD40 modules arranged in two seven-bladed β-propeller domains. The structure allowed for the mapping of conserved surface residues, and mutagenesis studies identified five residues that affected the ADF/cofilin-dependent Actin filament disassembly activity. Mutations of these residues, which reside in blades 3 and 4 in the N-terminal propeller domain, had significant effects on the disassembly activity but did not alter the barbed end capping activity. These data support a model in which this conserved surface of AIP1 plays a direct role in enhancing fragmentation/depolymerization of ADF/cofilin-bound Actin filaments but not in barbed end capping.
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microscopic evidence that Actin interActing protein 1 actively disassembles Actin Depolymerizing Factor cofilin bound Actin filaments
Journal of Biological Chemistry, 2004Co-Authors: Kurato MohriAbstract:Abstract Actin-Depolymerizing Factor (ADF)/cofilin and gelsolin are the two major Factors to enhance Actin filament disassembly. Actin-interActing protein 1 (AIP1) enhances fragmentation of ADF/cofilin-bound filaments and caps the barbed ends. However, the mechanism by which AIP1 disassembles ADF/cofilin-bound filaments is not clearly understood. Here, we directly observed the effects of these proteins on filamentous Actin by fluorescence microscopy and gained novel insight into the function of ADF/cofilin and AIP1. ADF/cofilin severed filaments and AIP1 strongly enhanced disassembly at nanomolar concentrations. However, gelsolin, gelsolin-Actin complex, or cytochalasin D did not enhance disassembly by ADF/cofilin, suggesting that the strong activity of AIP1 cannot be explained by simple barbed end capping. Barbed end capping by ADF/cofilin and AIP1 was weak and allowed filament elongation, whereas gelsolin or gelsolin-Actin complex strongly capped and inhibited elongation. These results suggest that AIP has an active role in filament severing or depolymerization and that ADF/cofilin and AIP1 are distinct from gelsolin in modulating filament elongation.
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Microscopic Evidence That Actin-interActing Protein 1 Actively Disassembles Actin-Depolymerizing Factor/Cofilin-bound Actin Filaments
Journal of Biological Chemistry, 2004Co-Authors: Kurato MohriAbstract:Abstract Actin-Depolymerizing Factor (ADF)/cofilin and gelsolin are the two major Factors to enhance Actin filament disassembly. Actin-interActing protein 1 (AIP1) enhances fragmentation of ADF/cofilin-bound filaments and caps the barbed ends. However, the mechanism by which AIP1 disassembles ADF/cofilin-bound filaments is not clearly understood. Here, we directly observed the effects of these proteins on filamentous Actin by fluorescence microscopy and gained novel insight into the function of ADF/cofilin and AIP1. ADF/cofilin severed filaments and AIP1 strongly enhanced disassembly at nanomolar concentrations. However, gelsolin, gelsolin-Actin complex, or cytochalasin D did not enhance disassembly by ADF/cofilin, suggesting that the strong activity of AIP1 cannot be explained by simple barbed end capping. Barbed end capping by ADF/cofilin and AIP1 was weak and allowed filament elongation, whereas gelsolin or gelsolin-Actin complex strongly capped and inhibited elongation. These results suggest that AIP has an active role in filament severing or depolymerization and that ADF/cofilin and AIP1 are distinct from gelsolin in modulating filament elongation.
R Ichard B. Meagher - One of the best experts on this subject based on the ideXlab platform.
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phylogenetic patterns of codon evolution in the Actin Depolymerizing Factor cofilin adf cfl gene family
PLOS ONE, 2015Co-Authors: Eileen M Royzokan, Kelly A Dyer, R Ichard B. MeagherAbstract:The Actin-Depolymerizing Factor/cofilin (ADF/CFL) gene family encodes a diverse group of relatively small proteins. Once known strictly as modulators of Actin filament dynamics, recent research has demonstrated that these proteins are involved in a variety of cellular processes, from signal transduction to the cytonuclear trafficking of Actin. In both plant and animal lineages, expression patterns of paralogs in the ADF/CFL gene family vary among tissue types and developmental stages. In this study we use computational approaches to investigate the evolutionary forces responsible for the diversification of the ADF/CFL gene family. Estimating the rate of non-synonymous to synonymous mutations (dN/dS) across phylogenetic lineages revealed that the majority of ADF/CFL codon positions were under strong purifying selection, with rare episodic events of accelerated protein evolution. In both plants and animals these instances of accelerated evolution were ADF/CFL subclass specific, and all of the sites under selection were located in regions of the protein that could serve in new functional roles. We suggest these sites may have been important in the functional diversification of ADF/CFL proteins.
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Phylogenetic Patterns of Codon Evolution in the Actin-Depolymerizing Factor/COFILIN (ADF/CFL) Gene Family.
PLOS ONE, 2015Co-Authors: Eileen M. Roy-zokan, Kelly A Dyer, R Ichard B. MeagherAbstract:The Actin-Depolymerizing Factor/cofilin (ADF/CFL) gene family encodes a diverse group of relatively small proteins. Once known strictly as modulators of Actin filament dynamics, recent research has demonstrated that these proteins are involved in a variety of cellular processes, from signal transduction to the cytonuclear trafficking of Actin. In both plant and animal lineages, expression patterns of paralogs in the ADF/CFL gene family vary among tissue types and developmental stages. In this study we use computational approaches to investigate the evolutionary forces responsible for the diversification of the ADF/CFL gene family. Estimating the rate of non-synonymous to synonymous mutations (dN/dS) across phylogenetic lineages revealed that the majority of ADF/CFL codon positions were under strong purifying selection, with rare episodic events of accelerated protein evolution. In both plants and animals these instances of accelerated evolution were ADF/CFL subclass specific, and all of the sites under selection were located in regions of the protein that could serve in new functional roles. We suggest these sites may have been important in the functional diversification of ADF/CFL proteins.
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arabidopsis Actin Depolymerizing Factor atadf4 mediates defense signal transduction triggered by the pseudomonas syringae effector avrpphb
Plant Physiology, 2009Co-Authors: Miaoying Tian, Faisal Chaudhry, R Ichard B. Meagher, Daniel R Ruzicka, Christopher J StaigerAbstract:The Actin cytoskeleton has been implicated in plant defenses against pathogenic fungi and oomycetes with limited, indirect evidence. To date, there are no reports linking Actin with resistance against phytopathogenic bacteria. The dynamic behavior of Actin filaments is regulated by a diverse array of Actin-binding proteins, among which is the Actin-Depolymerizing Factor (ADF) family of proteins. Here, we demonstrate that Actin dynamics play a role in the activation of gene-for-gene resistance in Arabidopsis (Arabidopsis thaliana) following inoculation with the phytopathogenic bacterium Pseudomonas syringae pv tomato. Using a reverse genetics approach, we explored the roles of Arabidopsis ADFs in plant defenses. AtADF4 was identified as being specifically required for resistance triggered by the effector AvrPphB but not AvrRpt2 or AvrB. Recombinant AtADF4 bound to monomeric Actin (G-Actin) with a marked preference for the ADP-loaded form and inhibited the rate of nucleotide exchange on G-Actin, indicating that AtADF4 is a bona fide Actin-Depolymerizing Factor. Exogenous application of the Actin-disrupting agent cytochalasin D partially rescued the Atadf4 mutant in the AvrPphB-mediated hypersensitive response, demonstrating that AtADF4 mediates defense signaling through modification of the Actin cytoskeleton. Unlike the mechanism by which the Actin cytoskeleton confers resistance against fungi and oomycetes, AtADF4 is not involved in resistance against pathogen entry. Collectively, this study identifies AtADF4 as a novel component of the plant defense signaling pathway and provides strong evidence for Actin dynamics as a primary component that orchestrates plant defenses against P. syringae.
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Arabidopsis Actin-Depolymerizing Factor AtADF4 Mediates Defense Signal Transduction Triggered by
2009Co-Authors: Miaoying Tian, Faisal Chaudhry, R. Ruzicka, R Ichard B. Meagher, Christopher J StaigerAbstract:The Actin cytoskeleton has been implicated in plant defenses against pathogenic fungi and oomycetes with limited, indirect evidence. To date, there are no reports linking Actin with resistance against phytopathogenic bacteria. The dynamic behavior of Actin filaments is regulated by a diverse array of Actin-binding proteins, among which is the Actin-Depolymerizing Factor (ADF) family of proteins. Here, we demonstrate that Actin dynamics play a role in the activation of gene-for-gene resistance in Arabidopsis (Arabidopsis thaliana) following inoculation with the phytopathogenic bacterium Pseudomonas syringae pv tomato. Using a reverse genetics approach, we explored the roles of Arabidopsis ADFs in plant defenses. AtADF4 was identified as being specifically required for resistance triggered by the effector AvrPphB but not AvrRpt2 or AvrB. Recombinant AtADF4 bound to monomeric Actin (G-Actin) with a marked preference for the ADP-loaded form and inhibited the rate of nucleotide exchange on G-Actin, indicating that AtADF4 is a bona fide Actin-Depolymerizing Factor. Exogenous application of the Actindisrupting agent cytochalasin D partially rescued the Atadf4 mutant in the AvrPphB-mediated hypersensitive response, demonstrating that AtADF4 mediates defense signaling through modification of the Actin cytoskeleton. Unlike the mechanism by which the Actin cytoskeleton confers resistance against fungi and oomycetes, AtADF4 is not involved in resistance against pathogen entry. Collectively, this study identifies AtADF4 as a novel component of the plant defense signaling pathway and provides strong evidence for Actin dynamics as a primary component that orchestrates plant defenses against P. syringae.
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the ancient subclasses of arabidopsis Actin Depolymerizing Factor genes exhibit novel and differential expression
Plant Journal, 2007Co-Authors: Daniel R Ruzicka, Muthugapatti K Kandasamy, Elizabeth C Mckinney, Brunilis Burgosrivera, R Ichard B. MeagherAbstract:SummaryThe Actin Depolymerizing Factor (ADF) gene family of Arabidopsis thaliana encodes 11 functional proteinisovariants in four ancient subclasses. We report the characterization of the tissue-specific and developmentalexpressionofallArabidopsisADFgenesandthesubcellularlocalizationofseveralproteinisovariants.Thefoursubclasses exhibited distinct expression patterns as examined by qRT-PCR and histochemical assays of a GUSreporter gene under the control of individual ADF regulatory sequences. Subclass I ADFs were expressedstrongly and constitutively in all vegetative and reproductive tissues except pollen. Subclass II ADFs wereexpressed specifically in mature pollen and pollen tubes or root epidermal trichoblast cells and root hairs, andthese patterns evolved from an ancient dual expression pattern comprised of both polar tip growth cell types,still observed in the monocot Oryza sativa. Subclass III ADFs were expressed weakly in vegetative tissues, butwere strongest in fast growing and/or differentiating cells including callus, emerging leaves, and meristemregions. The single subclass IV ADF was constitutively expressed at moderate levels in all tissues, includingpollen. Immunocytochemical analysis with subclass-specific monoclonal antibodies demonstrated thatsubclass I isovariants localize to both the cytoplasm and the nucleus of leaf cells, while subclass II isovariantspredominantlylocalizetothecytoplasmatthetipregionofelongatingroothairsandpollentubes.ThedistinctexpressionpatternsoftheADFsubclassessupportamodelofADFsco-evolvingwiththeancientanddivergentActin isovariants.Keywords: Actin Depolymerizing Factor, Actin cytoskeleton, GUS, isovariant dynamics, subfunctionalization.IntroductionThe Actin cytoskeleton plays an essential role in manycellular processes, and its diverse functions include cyto-plasmic organization, establishment of cell polarity, cellelongation, polar tip growth, intracellular trafficking, andcytokinesis (Meagher and Williamson, 1994; Pollard et al.,2000; Staiger, 2000; Wasteneys and Galway, 2003). Tofunction as a coordinated network that rapidly responds tomultiple cellular activities, Actin filaments are dynamicallyreorganized and remodeled by multiple Actin bindingproteins (ABPs) (Borisy and Svitkina, 2000; Paavilainenet al., 2004). In higher plants, the Actin cytoskeleton com-prises multiple Actin isovariants phylogenetically groupedinto two ancient subclasses (McDowell et al., 1996) whosevegetative and reproductive members pre-date the originof angiosperms (Meagher et al., 1999a,b). More than adozen ABPs are in similarly encoded diverse and ancientfamilies (Klahre et al., 2000; Deeks et al., 2002; Kandasamyet al., 2002a; Meagher and Fechheimer, 2003; Cvrckovaet al., 2004) suggesting a remarkable complexity of net-worked interactions surrounding the ancient Actins. Thehypothesis of isovariant dynamics proposes that differ-ences in gene regulation and protein structure amongco-expressed family members increase the dynamiccapacity of the Actin cytoskeleton (Meagher et al., 1999a).Support for this comes from the functional non-equiva-lency of the ancient classes of Arabidopsis Actins demon-strated by the dramatic phenotypes created by the ectopicexpression of a reproductive Actin in vegetative tissues(Gilliland et al., 2002; Kandasamy et al., 2002b). It is likelythat ABP gene families also demonstrate equivalent
Pekka Lappalainen - One of the best experts on this subject based on the ideXlab platform.
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Actin-Depolymerizing Factor homology domain: A conserved fold performing diverse roles in cytoskeletal dynamics †
Cytoskeleton, 2011Co-Authors: Minna Poukkula, Elena Kremneva, Martina Serlachius, Pekka LappalainenAbstract:Actin filaments form contractile and protrusive structures that play central roles in many processes such as cell migration, morphogenesis, endocytosis, and cytokinesis. During these processes, the dynamics of the Actin filaments are precisely regulated by a large array of Actin-binding proteins. The Actin-Depolymerizing Factor homology (ADF-H) domain is a structurally conserved protein motif, which promotes cytoskeletal dynamics by interActing with monomeric and/or filamentous Actin, and with the Arp2/3 complex. Despite their structural homology, the five classes of ADF-H domain proteins display distinct biochemical activities and cellular roles, only parts of which are currently understood. ADF/cofilin promotes disassembly of aged Actin filaments, whereas twinfilin inhibits Actin filament assembly via sequestering Actin monomers and interActing with filament barbed ends. GMF does not interact with Actin, but instead binds Arp2/3 complex and promotes dissociation of Arp2/3-mediated filament branches. Abp1 and drebrin are multidomain proteins that interact with Actin filaments and regulate the activities of other proteins during various Actin-dependent processes. The exact function of coactosin is currently incompletely understood. In this review article, we discuss the biochemical functions, cellular roles, and regulation of the five groups of ADF-H domain proteins. © 2011 Wiley-Liss, Inc.
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Actin Depolymerizing Factor homology domain a conserved fold performing diverse roles in cytoskeletal dynamics
Cytoskeleton, 2011Co-Authors: Minna Poukkula, Elena Kremneva, Martina Serlachius, Pekka LappalainenAbstract:Actin filaments form contractile and protrusive structures that play central roles in many processes such as cell migration, morphogenesis, endocytosis, and cytokinesis. During these processes, the dynamics of the Actin filaments are precisely regulated by a large array of Actin-binding proteins. The Actin-Depolymerizing Factor homology (ADF-H) domain is a structurally conserved protein motif, which promotes cytoskeletal dynamics by interActing with monomeric and/or filamentous Actin, and with the Arp2/3 complex. Despite their structural homology, the five classes of ADF-H domain proteins display distinct biochemical activities and cellular roles, only parts of which are currently understood. ADF/cofilin promotes disassembly of aged Actin filaments, whereas twinfilin inhibits Actin filament assembly via sequestering Actin monomers and interActing with filament barbed ends. GMF does not interact with Actin, but instead binds Arp2/3 complex and promotes dissociation of Arp2/3-mediated filament branches. Abp1 and drebrin are multidomain proteins that interact with Actin filaments and regulate the activities of other proteins during various Actin-dependent processes. The exact function of coactosin is currently incompletely understood. In this review article, we discuss the biochemical functions, cellular roles, and regulation of the five groups of ADF-H domain proteins. © 2011 Wiley-Liss, Inc.
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structure of the Actin Depolymerizing Factor homology domain in complex with Actin
Journal of Cell Biology, 2008Co-Authors: Ville O Paavilainen, Esko Oksanen, Adrian Goldman, Pekka LappalainenAbstract:Actin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among the central cytoskeletal regulators are Actin-Depolymerizing Factor (ADF)/cofilin, which depolymerizes Actin filaments, and twinfilin, which sequesters Actin monomers and caps filament barbed ends. Both interact with Actin through an ADF homology (ADF-H) domain, which is also found in several other Actin-binding proteins. However, in the absence of an atomic structure for the ADF-H domain in complex with Actin, the mechanism by which these proteins interact with Actin has remained unknown. Here, we present the crystal structure of twinfilin's C-terminal ADF-H domain in complex with an Actin monomer. This domain binds between Actin subdomains 1 and 3 through an interface that is conserved among ADF-H domain proteins. Based on this structure, we suggest a mechanism by which ADF/cofilin and twinfilin inhibit nucleotide exchange of Actin monomers and present a model for how ADF/cofilin induces filament depolymerization by weakening intrafilament interactions.
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Actin Depolymerizing Factor and cofilin 1 play overlapping roles in promoting rapid f Actin depolymerization in mammalian nonmuscle cells
Molecular Biology of the Cell, 2004Co-Authors: Pirta Hotulainen, Maria K Vartiainen, Eija Paunola, Pekka LappalainenAbstract:Actin-Depolymerizing Factor (ADF)/cofilins are small Actin-binding proteins found in all eukaryotes. In vitro, ADF/cofilins promote Actin dynamics by Depolymerizing and severing Actin filaments. However, whether ADF/cofilins contribute to Actin dynamics in cells by disassembling “old” Actin filaments or by promoting Actin filament assembly through their severing activity is a matter of controversy. Analysis of mammalian ADF/cofilins is further complicated by the presence of multiple isoforms, which may contribute to Actin dynamics by different mechanisms. We show that two isoforms, ADF and cofilin-1, are expressed in mouse NIH 3T3, B16F1, and Neuro 2A cells. Depleting cofilin-1 and/or ADF by siRNA leads to an accumulation of F-Actin and to an increase in cell size. Cofilin-1 and ADF seem to play overlapping roles in cells, because the knockdown phenotype of either protein could be rescued by overexpression of the other one. Cofilin-1 and ADF knockdown cells also had defects in cell motility and cytokinesis, and these defects were most pronounced when both ADF and cofilin-1 were depleted. Fluorescence recovery after photobleaching analysis and studies with an Actin monomer-sequestering drug, latrunculin-A, demonstrated that these phenotypes arose from diminished Actin filament depolymerization rates. These data suggest that mammalian ADF and cofilin-1 promote cytoskeletal dynamics by Depolymerizing Actin filaments and that this activity is critical for several processes such as cytokinesis and cell motility.
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the three mouse Actin Depolymerizing Factor cofilins evolved to fulfill cell type specific requirements for Actin dynamics
Molecular Biology of the Cell, 2002Co-Authors: Maria K Vartiainen, Tuija Mustonen, Pieta K Mattila, Pauli J Ojala, Irma Thesleff, Juha Partanen, Pekka LappalainenAbstract:Actin-Depolymerizing Factor (ADF)/cofilins are essential regulators of Actin filament turnover. Several ADF/cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/cofilins exist in mouse and most likely in all other mammalian species. Northern blot and in situ hybridization analyses demonstrate that cofilin-1 is expressed in most cell types of embryos and adult mice. Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia. Although the three mouse ADF/cofilins do not show Actin isoform specificity, they all depolymerize platelet Actin filaments more efficiently than muscle Actin. Furthermore, these ADF/cofilins are biochemically different. The epithelial-specific ADF is the most efficient in turning over Actin filaments and promotes a stronger pH-dependent Actin filament disassembly than the two other isoforms. The muscle-specific cofilin-2 has a weaker Actin filament depolymerization activity and displays a 5-10-fold higher affinity for ATP-Actin monomers than cofilin-1 and ADF. In steady-state assays, cofilin-2 also promotes filament assembly rather than disassembly. Taken together, these data suggest that the three biochemically distinct mammalian ADF/cofilin isoforms evolved to fulfill specific requirements for Actin filament dynamics in different cell types.
