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Pekka Lappalainen - One of the best experts on this subject based on the ideXlab platform.
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Mechanism of synergistic Actin Filament pointed end depolymerization by cyclase-associated protein and cofilin
Nature Communications, 2019Co-Authors: Tommi Kotila, Hugo Wioland, Giray Enkavi, Konstantin Kogan, Ilpo Vattulainen, Antoine Jegou, Guillaume Romet-lemonne, Pekka LappalainenAbstract:The ability of cells to generate forces through Actin Filament turnover was an early adaptation in evolution. While much is known about how Actin Filaments grow, mechanisms of their disassembly are incompletely understood. The best-characterized Actin disassembly factors are the cofilin family proteins, which increase cytoskeletal dynamics by severing Actin Filaments. However, the mechanism by which severed Actin Filaments are recycled back to monomeric form has remained enigmatic. We report that cyclase-associated-protein (CAP) works in synergy with cofilin to accelerate Actin Filament depolymerization by nearly 100-fold. Structural work uncovers the molecular mechanism by which CAP interacts with Actin Filament pointed end to destabilize the interface between terminal Actin subunits, and subsequently recycles the newly-depolymerized Actin monomer for the next round of Filament assembly. These findings establish CAP as a molecular machine promoting rapid Actin Filament depolymerization and monomer recycling, and explain why CAP is critical for Actindependent processes in all eukaryotes.
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Tropomyosin Isoforms Specify Functionally Distinct Actin Filament Populations In Vitro
Current Biology - CB, 2017Co-Authors: Gergana Gateva, Elena Kremneva, Alphée Michelot, Tommi Kotila, Konstantin Kogan, Laurène Gressin, Theresia Reindl, Peter Gunning, Dietmar Manstein, Pekka LappalainenAbstract:Actin Filaments assemble into a variety of networks to provide force for diverse cellular processes [1]. Tropomyosins are coiled-coil dimers that form head-to-tail polymers along Actin Filaments and regulate interactions of other proteins, including Actin-depolymerizing factor (ADF)/cofilins and myosins, with Actin [2-5]. In mammals, >40 tropomyosin isoforms can be generated through alternative splicing from four tropomyosin genes. Different isoforms display non-redundant functions and partially non-overlapping localization patterns, for example within the stress fiber network [6, 7]. Based on cell biological studies, it was thus proposed that tropomyosin isoforms may specify the functional properties of different Actin Filament populations [2]. To test this hypothesis, we analyzed the properties of Actin Filaments decorated by stress-fiber-associated tropomyosins (Tpm1.6, Tpm1.7, Tpm2.1, Tpm3.1, Tpm3.2, and Tpm4.2). These proteins bound F-Actin with high affinity and competed with α-Actinin for Actin Filament binding. Importantly, total internal reflection fluorescence (TIRF) microscopy of fluorescently tagged proteins revealed that most tropomyosin isoforms cannot co-polymerize with each other on Actin Filaments. These isoforms also bind Actin with different dynamics, which correlate with their effects on Actin-binding proteins. The long isoforms Tpm1.6 and Tpm1.7 displayed stable interactions with Actin Filaments and protected Filaments from ADF/cofilin-mediated disassembly, but did not activate non-muscle myosin IIa (NMIIa). In contrast, the short isoforms Tpm3.1, Tpm3.2, and Tpm4.2 displayed rapid dynamics on Actin Filaments and stimulated the ATPase activity of NMIIa, but did not efficiently protect Filaments from ADF/cofilin. Together, these data provide experimental evidence that tropomyosin isoforms segregate to different Actin Filaments and specify functional properties of distinct Actin Filament populations.
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Actin Filament Structures in Migrating Cells
Handbook of experimental pharmacology, 2016Co-Authors: Jaakko I. Lehtimäki, Markku Hakala, Pekka LappalainenAbstract:Cell migration is necessary for several developmental processes in multicellular organisms. Furthermore, many physiological processes such as wound healing and immunological events in adult animals are dependent on cell migration. Consequently, defects in cell migration are linked to various diseases including immunological disorders as well as cancer progression and metastasis formation. Cell migration is driven by specific protrusive and contractile Actin Filament structures, but the types and relative contributions of these Actin Filament arrays vary depending on the cell type and the environment of the cell. In this chapter, we introduce the most important Actin Filament structures that contribute to mesenchymal and amoeboid cell migration modes and discuss the mechanisms by which the assembly and turnover of these structures are controlled by various Actin-binding proteins.
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tropomyosin master regulator of Actin Filament function in the cytoskeleton
Journal of Cell Science, 2015Co-Authors: Peter W Gunning, Pekka Lappalainen, Edna C Hardeman, Daniel P MulvihillAbstract:Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual Actin Filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of Actin Filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal Actin Filament contains a homopolymer of Tpm homodimers, resulting in a Filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct Actin Filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of Actin Filament nucleators can specify which Tpm isoform is added to the growing Actin Filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of Actin Filaments with myosin motors and Actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of Actin Filament specified by their Tpm composition. This allows the cell to specify Actin Filament function in time and space by simply specifying their Tpm isoform composition.
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Tropomyosin – master regulator of Actin Filament function in the cytoskeleton
Journal of cell science, 2015Co-Authors: Peter W Gunning, Pekka Lappalainen, Edna C Hardeman, Daniel P MulvihillAbstract:Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual Actin Filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of Actin Filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal Actin Filament contains a homopolymer of Tpm homodimers, resulting in a Filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct Actin Filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of Actin Filament nucleators can specify which Tpm isoform is added to the growing Actin Filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of Actin Filaments with myosin motors and Actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of Actin Filament specified by their Tpm composition. This allows the cell to specify Actin Filament function in time and space by simply specifying their Tpm isoform composition.
Thomas D Pollard - One of the best experts on this subject based on the ideXlab platform.
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force and phosphate release from arp2 3 complex promote dissociation of Actin Filament branches
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Nandan G Pandit, Wenxiang Cao, Thomas D Pollard, J P Bibeau, Eric M Johnsonchavarria, Edwin W Taylor, Enrique M De La CruzAbstract:Networks of branched Actin Filaments formed by Arp2/3 complex generate and experience mechanical forces during essential cellular functions, including cell motility and endocytosis. External forces regulate the assembly and architecture of branched Actin networks both in vitro and in cells. Considerably less is known about how mechanical forces influence the disassembly of Actin Filament networks, specifically, the dissociation of branches. We used microfluidics to apply force to branches formed from purified muscle Actin and fission yeast Arp2/3 complex and observed debranching events in real time with total internal reflection fluorescence microscopy. Low forces in the range of 0 pN to 2 pN on branches accelerated their dissociation from mother Filaments more than two orders of magnitude, from hours to <1 min. Neither force on the mother Filament nor thermal fluctuations in mother Filament shape influenced debranching. Arp2/3 complex at branch junctions adopts two distinct mechanical states with different sensitivities to force, which we name "young/strong" and "old/weak." The "young/strong" state 1 has adenosine 5'-diphosphate (ADP)-P i bound to Arp2/3 complex. Phosphate release converts Arp2/3 complex into the "old/weak" state 2 with bound ADP, which is 20 times more sensitive to force than state 1. Branches with ADP-Arp2/3 complex are more sensitive to debranching by fission yeast GMF (glia maturation factor) than branches with ADP-P i -Arp2/3 complex. These findings suggest that aging of branch junctions by phosphate release from Arp2/3 complex and mechanical forces contribute to disassembling "old" Actin Filament branches in cells.
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gating mechanisms during Actin Filament elongation by formins
eLife, 2018Co-Authors: Fikret Aydin, Thomas D Pollard, Naomi Courtemanche, Gregory A VothAbstract:Formins play an important role in the polymerization of unbranched Actin Filaments, and particular formins slow elongation by 5-95%. We studied the interactions between Actin and the FH2 domains of formins Cdc12, Bni1 and mDia1 to understand the factors underlying their different rates of polymerization. All-atom molecular dynamics simulations revealed two factors that influence Actin Filament elongation and correlate with the rates of elongation. First, FH2 domains can sterically block the addition of new Actin subunits. Second, FH2 domains flatten the helical twist of the terminal Actin subunits, making the end less favorable for subunit addition. Coarse-grained simulations over longer time scales support these conclusions. The simulations show that Filaments spend time in states that either allow or block elongation. The rate of elongation is a time-average of the degree to which the formin compromises subunit addition rather than the formin-Actin complex literally being in 'open' or 'closed' states.
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mathematical modeling of endocytic Actin patch kinetics in fission yeast disassembly requires release of Actin Filament fragments
Molecular Biology of the Cell, 2010Co-Authors: Vladimir Sirotkin, Julien Berro, Thomas D PollardAbstract:We used the dendritic nucleation hypothesis to formulate a mathematical model of the assembly and disassembly of Actin Filaments at sites of clathrin-mediated endocytosis in fission yeast. We used the wave of active WASp recruitment at the site of the patch formation to drive assembly reactions after activation of Arp2/3 complex. Capping terminated Actin Filament elongation. Aging of the Filaments by ATP hydrolysis and gamma-phosphate dissociation allowed Actin Filament severing by cofilin. The model could simulate the assembly and disassembly of Actin and other Actin patch proteins using measured cytoplasmic concentrations of the proteins. However, to account quantitatively for the numbers of proteins measured over time in the accompanying article (Sirotkin et al., 2010, MBoC 21: 2792-2802), two reactions must be faster in cells than in vitro. Conditions inside the cell allow capping protein to bind to the barbed ends of Actin Filaments and Arp2/3 complex to bind to the sides of Filaments faster than the purified proteins in vitro. Simulations also show that depolymerization from pointed ends cannot account for rapid loss of Actin Filaments from patches in 10 s. An alternative mechanism consistent with the data is that severing produces short fragments that diffuse away from the patch.
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Structure and Dynamics of the Actin Filament
Journal of molecular biology, 2009Co-Authors: Jim Pfaendtner, Thomas D Pollard, Edward Lyman, Gregory A VothAbstract:We used all-atom molecular dynamics simulations to investigate the structure and properties of the Actin Filament, starting with either the recent Oda model or the older Holmes model. Simulations of monomeric and polymerized Actin show that polymerization changes the nucleotide-binding cleft, bringing together the Q137 side chain and bound ATP in a way that may enhance the ATP hydrolysis rate in the Filament. Simulations with different bound nucleotides and conformations of the DNase I binding loop show that the persistence length of the Filament depends only on loop conformation. Computational modeling reveals how bound phalloidin stiffens Actin Filaments and inhibits the release of gamma-phosphate from ADP-P(i) Actin.
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pathway of Actin Filament branch formation by arp2 3 complex
Journal of Biological Chemistry, 2008Co-Authors: Christopher C Beltzner, Thomas D PollardAbstract:A spectroscopic assay using pyrene-labeled fission yeast Arp2/3 complex revealed that the complex binds to and dissociates from Actin Filaments extremely slowly with or without the nucleation-promoting factor fission yeast Wsp1-VCA. Wsp1-VCA binds both Arp2/3 complex and Actin monomers with high affinity. These two ligands have only modest impacts on the interaction of the other ligand with VCA. Simulations of a mathematical model based on the kinetic parameters determined in this study and elsewhere account for the full time course of Actin polymerization in the presence of Arp2/3 complex and Wsp1-VCA and show that an activation step, postulated to follow binding of a ternary complex of Arp2/3 complex, a bound nucleation-promoting factor, and an Actin monomer to an Actin Filament, has a rate constant at least 0.15 s(-1). Kinetic parameters determined in this study constrain the process of Actin Filament branch formation during cellular motility to one main pathway.
Peter W Gunning - One of the best experts on this subject based on the ideXlab platform.
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Recruitment Kinetics of Tropomyosin Tpm3.1 to Actin Filament Bundles in the Cytoskeleton Is Independent of Actin Filament Kinetics.
PloS one, 2016Co-Authors: Mark Appaduray, Peter W Gunning, Andrius Masedunskas, Nicole S. Bryce, Christine A. Lucas, Sean C. Warren, Paul Timpson, Jeffrey H. Stear, Edna C HardemanAbstract:The Actin cytoskeleton is a dynamic network of Filaments that is involved in virtually every cellular process. Most Actin Filaments in metazoa exist as a co-polymer of Actin and tropomyosin (Tpm) and the function of an Actin Filament is primarily defined by the specific Tpm isoform associated with it. However, there is little information on the interdependence of these co-polymers during Filament assembly and disassembly. We addressed this by investigating the recovery kinetics of fluorescently tagged isoform Tpm3.1 into Actin Filament bundles using FRAP analysis in cell culture and in vivo in rats using intracellular intravital microscopy, in the presence or absence of the Actin-targeting drug jasplakinolide. The mobile fraction of Tpm3.1 is between 50% and 70% depending on whether the tag is at the C- or N-terminus and whether the analysis is in vivo or in cultured cells. We find that the continuous dynamic exchange of Tpm3.1 is not significantly impacted by jasplakinolide, unlike tagged Actin. We conclude that tagged Tpm3.1 may be able to undergo exchange in Actin Filament bundles largely independent of the assembly and turnover of Actin.
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tropomyosin master regulator of Actin Filament function in the cytoskeleton
Journal of Cell Science, 2015Co-Authors: Peter W Gunning, Pekka Lappalainen, Edna C Hardeman, Daniel P MulvihillAbstract:Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual Actin Filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of Actin Filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal Actin Filament contains a homopolymer of Tpm homodimers, resulting in a Filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct Actin Filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of Actin Filament nucleators can specify which Tpm isoform is added to the growing Actin Filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of Actin Filaments with myosin motors and Actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of Actin Filament specified by their Tpm composition. This allows the cell to specify Actin Filament function in time and space by simply specifying their Tpm isoform composition.
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Tropomyosin – master regulator of Actin Filament function in the cytoskeleton
Journal of cell science, 2015Co-Authors: Peter W Gunning, Pekka Lappalainen, Edna C Hardeman, Daniel P MulvihillAbstract:Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual Actin Filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of Actin Filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal Actin Filament contains a homopolymer of Tpm homodimers, resulting in a Filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct Actin Filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of Actin Filament nucleators can specify which Tpm isoform is added to the growing Actin Filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of Actin Filaments with myosin motors and Actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of Actin Filament specified by their Tpm composition. This allows the cell to specify Actin Filament function in time and space by simply specifying their Tpm isoform composition.
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Specification of Actin Filament Function and Molecular Composition by Tropomyosin Isoforms
Molecular biology of the cell, 2003Co-Authors: Nicole S. Bryce, Edna C Hardeman, Galina Schevzov, Vicki Ferguson, Justin M. Percival, Jim J.-c. Lin, Fumio Matsumura, James R. Bamburg, Peter L. Jeffrey, Peter W GunningAbstract:The specific functions of greater than 40 vertebrate nonmuscle tropomyosins (Tms) are poorly understood. In this article we have tested the ability of two Tm isoforms, TmBr3 and the human homologue of Tm5 (hTM5NM1), to regulate Actin Filament function. We found that these Tms can differentially alter Actin Filament organization, cell size, and shape. hTm5NM1 was able to recruit myosin II into stress fibers, which resulted in decreased lamellipodia and cellular migration. In contrast, TmBr3 transfection induced lamellipodial formation, increased cellular migration, and reduced stress fibers. Based on coimmunoprecipitation and colocalization studies, TmBr3 appeared to be associated with Actin-depolymerizing factor/cofilin (ADF)-bound Actin Filaments. Additionally, the Tms can specifically regulate the incorporation of other Tms into Actin Filaments, suggesting that selective dimerization may also be involved in the control of Actin Filament organization. We conclude that Tm isoforms can be used to specify the functional properties and molecular composition of Actin Filaments and that spatial segregation of isoforms may lead to localized specialization of Actin Filament function.
Dyche R Mullins - One of the best experts on this subject based on the ideXlab platform.
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lc3 and strap regulate Actin Filament assembly by jmy during autophagosome formation
Journal of Cell Biology, 2019Co-Authors: Dyche R MullinsAbstract:During autophagy, Actin Filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two Actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to Actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY’s nuclear functions, on nonmotile vesicles with no associated Actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on Actin comet tails. LC3 enhances JMY’s de novo Actin nucleation activity via a cryptic Actin-binding sequence near JMY’s N terminus, and STRAP inhibits JMY’s ability to nucleate Actin and activate the Arp2/3 complex. Cytoplasmic STRAP negatively regulates autophagy. Finally, we use purified proteins to reconstitute LC3- and JMY-dependent Actin network formation on membranes and inhibition of network formation by STRAP. We conclude that LC3 and STRAP regulate JMY’s Actin assembly activities in trans during autophagy.
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interactions of adf cofilin arp2 3 complex capping protein and profilin in remodeling of branched Actin Filament networks
Current Biology, 2000Co-Authors: Laurent Blanchoin, Thomas D Pollard, Dyche R MullinsAbstract:Abstract Background: Cellular movements are powered by the assembly and disassembly of Actin Filaments. Actin dynamics are controlled by Arp2/3 complex, the Wiskott–Aldrich syndrome protein (WASp) and the related Scar protein, capping protein, profilin, and the Actin-depolymerizing factor (ADF, also known as cofilin). Recently, using an assay that both reveals the kinetics of overall reactions and allows visualization of Actin Filaments, we showed how these proteins co-operate in the assembly of branched Actin Filament networks. Here, we investigated how they work together to disassemble the networks. Results: Actin Filament branches formed by polymerization of ATP–Actin in the presence of activated Arp2/3 complex were found to be metastable, dissociating from the mother Filament with a half time of 500 seconds. The ADF/cofilin protein actophorin reduced the half time for both dissociation of γ-phosphate from ADP–P i –Actin Filaments and debranching to 30 seconds. Branches were stabilized by phalloidin, which inhibits phosphate dissociation from ADP–P i –Filaments, and by BeF 3 , which forms a stable complex with ADP and Actin. Arp2/3 complex capped pointed ends of ATP–Actin Filaments with higher affinity (K d ∼40nM) than those of ADP–Actin Filaments (K d ∼1μM), explaining why phosphate dissociation from ADP–P i –Filaments liberates branches. Capping protein prevented annealing of short Filaments after debranching and, with profilin, allowed Filaments to depolymerize at the pointed ends. Conclusions: The low affinity of Arp2/3 complex for the pointed ends of ADP–Actin makes Actin Filament branches transient. By accelerating phosphate dissociation, ADF/cofilin promotes debranching. Barbed-end capping proteins and profilin allow dissociated branches to depolymerize from their free pointed ends.
Daniel P Mulvihill - One of the best experts on this subject based on the ideXlab platform.
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tropomyosin master regulator of Actin Filament function in the cytoskeleton
Journal of Cell Science, 2015Co-Authors: Peter W Gunning, Pekka Lappalainen, Edna C Hardeman, Daniel P MulvihillAbstract:Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual Actin Filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of Actin Filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal Actin Filament contains a homopolymer of Tpm homodimers, resulting in a Filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct Actin Filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of Actin Filament nucleators can specify which Tpm isoform is added to the growing Actin Filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of Actin Filaments with myosin motors and Actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of Actin Filament specified by their Tpm composition. This allows the cell to specify Actin Filament function in time and space by simply specifying their Tpm isoform composition.
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Tropomyosin – master regulator of Actin Filament function in the cytoskeleton
Journal of cell science, 2015Co-Authors: Peter W Gunning, Pekka Lappalainen, Edna C Hardeman, Daniel P MulvihillAbstract:Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual Actin Filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of Actin Filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal Actin Filament contains a homopolymer of Tpm homodimers, resulting in a Filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct Actin Filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of Actin Filament nucleators can specify which Tpm isoform is added to the growing Actin Filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of Actin Filaments with myosin motors and Actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of Actin Filament specified by their Tpm composition. This allows the cell to specify Actin Filament function in time and space by simply specifying their Tpm isoform composition.
