Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments

Remedios, Cris G. dos; Chhabra, Deepak; Kekic, Murat; Dedova, Irina; Tsubakihara, Masako; Berry, Desirée A.; Nosworthy, Neil J.

doi:10.1152/physrev.00026.2002

Cited by 894 publications

(744 citation statements)

References 293 publications

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“…9). This completely changes the previous concept of pointed end organization, whereby one molecule of Tmod binds to one molecule of TM (4). This model should be subject to further investigations.…”

Section: Discussionmentioning

confidence: 58%

“…9 % polyacrylamide gels that were polymerized in the presence of 10% glycerol without SDS were used (24). To prepare complexes for loading onto gels, equimolar amounts of Tmod in the absence or presence of GlyTM1b [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Zip were mixed in a 1:2 molar ratio. For titration, stock solutions of tropomodulin and GlyTM1b [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Zip were mixed in different ratios in buffer containing 100 mM NaCl.…”

Section: Binding Experimentsmentioning

confidence: 99%

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Tropomodulin Binds Two Tropomyosins: A Novel Model for Actin Filament Capping

2006

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Tropomodulin, a tropomyosin-binding protein, caps the slow-growing (pointed) end of the actin filament regulating its dynamics. Tropomodulin, therefore, is important for determining cell morphology, cell movement, and muscle contraction. For the first time we show that one tropomodulin molecule simultaneously binds two tropomyosin molecules in a cooperative manner. On the basis of the tropomodulin solution structure and predicted secondary structure, we introduced a series of point mutations in regions important for tropomyosin-binding and actin-capping. Capping activity of these mutants was assayed by measuring actin polymerization using pyrene fluorescence. Using direct methods (circular dichroism and native gel-electrophoresis) for detecting tropomodulin/ tropomyosin binding, we localized the second tropomyosin-binding site to residues 109-144. Despite previous reports that the second binding site is for erythrocyte tropomyosin only, we found that both short non-muscle and long muscle α-tropomyosins bind there as well, though with different affinities. We propose a model for actin capping where one tropomodulin molecule can bind to two tropomyosin molecules at the pointed end. Keywordstropomodulin; tropomyosin; actin filament; pointed end Actin is a major component of the cell cytoskeleton and the sarcomeres of striated muscle, and plays a critical role in cell morphology, cell movement, and muscle contraction (1,2). It is known that actin filaments form vastly different structures in different cell types and in different locations within the cell. Regulation of the dynamics at actin's ends is of central importance in the assembly of these various structures. An actin filament has two distinct ends: a fastgrowing barbed end and a slow-growing pointed end (3). The exclusive properties of these ends are exploited by over 160 distinct actin binding proteins, including those that cap, sever, or cross-link filaments (4). Of particular interest is tropomodulin (Tmod), a tropomyosinbinding protein, which regulates actin filament dynamics by capping the pointed end.Tropomyosin (TM) is a two-chained coiled coil that binds head-to-tail (N to C terminus) along the length of both sides of actin filaments, spanning 6-7 actin monomers per TM molecule, depending on the isoform (5). There are a variety of TM isoforms encoded by different genes. The N-terminus of TM, which points towards the pointed end of the actin filament (6), is required for interaction with Tmod (7-9). Best known for its role in muscle contraction (10, 11), TM also regulates the stiffness of actin (12) and influences polymerization at the pointed To whom correspondence should be addressed: Alla S. Kostyukova, end (13,14). Tmod in combination with TM forms a cap at the pointed end, preventing addition or loss of G-actin (15-17).Tropomodulin, originally discovered as a TM-binding protein in erythrocyte membranes (18), is the only known pointed end specific capping protein (15). Presently, there are four known Tmod isoforms (16,19,20). These isofor...

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Section: Discussionmentioning

confidence: 58%

Section: Binding Experimentsmentioning

confidence: 99%

Tropomodulin Binds Two Tropomyosins: A Novel Model for Actin Filament Capping

2006

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“…The only known influences on these rates are proteins of the ADF/cofilin family, which are present at significant concentrations in cells, $20 lM. 1,12,14,44 Cofilins bind preferentially to ADP-bound subunits in actin filaments and accelerate depolymerization of these filaments by increasing the off-rate of ADP-actin subunits, 9 severing filaments to create more ends, 31 and increasing the Pi release rate on ADPAEPi-bound subunits. 5 However, it is not clear what the relative contributions of these three effects are and how they relate to the concentration of cofilin.…”

Section: Parameter Choicesmentioning

confidence: 99%

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

Bindschadler

McGrath

2007

Ann Biomed Eng

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Abstract-In this report we extend our recent mathematical formulation of the actin cycle model [Bindschadler et al. Biophys. J. 86 (2004) 2720] to predict the influence of key regulatory mechanisms on network-scale state variables estimable in live cell experiments. Specifically, we examine the influence of regulation by cofilin, profilin, capping protein and proteins that adjust filament number through nucleation and/or filament severing, on the higher order variables of average filament length, polymer fraction, and filament turnover rate. Importantly, we find that severing/ nucleation, the acceleration of ADP-subunit disassembly by cofilin, and the catalytic and shuttle functions of profilin have Ôsignature' effects on the higher order state variables. In this way, measurement of the state variables in live cells can allow inference of regulatory mechanism(s) underlying changes in cell state. Our results compare favorably to published data for endothelial cells undergoing a transition from non-motile confluent cells to highly motile subconfluent cells. The extension of our model to higher order state variables allows us to investigate other important issues such as the distinction between basic and higher order measures of filament dynamics, the influence of thymosin b4 on network state variables, the interplay between thymosin b4 and profilin, and the synergystic effects of cofilin and profilin.

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“…Basically, filamentous (F-) actin is generated by the linear assembly of globular (G-) actin monomers into polymeric structures. Within the cells, actin filament (AF) assembly and disassembly are facilitated at spatial and temporal levels by a plethora of actin-binding proteins (ABPs), including nucleating, depolymerizing, severing, capping, F-actin stabilizing and G-actin sequestering proteins [Dos Remedios et al, 2003]. Among the repertoire of actin-binding proteins (ABPs) that regulate AF dynamics, one may cite key players such as the Arp2/3 complex and formins, which direct the initiation of new branched and unbranched filaments respectively [Pollard, 2007], as well as the actindepolymerizing factor (ADF)/cofilin family members, which increase filament turnover [Bamburg et al, 1999;Van Troys et al, 2008].…”

Section: Introductionmentioning

confidence: 99%

Actin bundling in plants

Thomas

Tholl

Moes

et al. 2009

Cell Motil. Cytoskeleton

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Tight regulation of plant actin cytoskeleton organization and dynamics is crucial for numerous cellular processes including cell division, expansion and intracellular trafficking. Among the various actin regulatory proteins, actin-bundling proteins trigger the formation of bundles composed of several parallel actin filaments closely packed together. Actin bundles are present in virtually all plant cells, but their biological roles have rarely been addressed directly. However, decades of research in the plant cytoskeleton field yielded a bulk of data from which an overall picture of the functions supplied by actin bundles in plant cells emerges. Although plants lack several equivalents of animal actin-bundling proteins, they do possess major bundler classes including fimbrins, villins and formins. The existence of additional players is not excluded as exemplified by the recent characterization of plant LIM proteins, which trigger the formation of actin bundles both in vitro and in vivo. This apparent functional redundancy likely reflects the need for plant cells to engineer different types of bundles that act at different sub-cellular locations and exhibit specific function-related properties. By surveying information regarding the properties of plant actin bundles and their associated bundling proteins, the present review aims at clarifying why and how plants make actin bundles. Cell Motil. Cytoskeleton 66: 940-957, 2009. '

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Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments

Cited by 894 publications

References 293 publications

Tropomodulin Binds Two Tropomyosins: A Novel Model for Actin Filament Capping

Tropomodulin Binds Two Tropomyosins: A Novel Model for Actin Filament Capping

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

Actin bundling in plants

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