How profilin promotes actin filament assembly in the presence of thymosin β4

Pantaloni, Dominique; Carlier, Marie-France

doi:10.1016/0092-8674(93)90544-z

Cited by 517 publications

(529 citation statements)

References 36 publications

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“…E04 -03-0225. for profilin (Boquet et al, 2000;Hertzog et al, 2002). Indeed, profilin serves as a polymerization catalyst by capturing an actin monomer and ushering the actin onto the growing filament barbed end as a 1:1 profilin:actin complex, whereupon profilin itself is released (Pantaloni and Carlier, 1993;Kang et al, 1999). Ciboulot is suggested to act on elongation via the same mechanism as profilin by forming a 1:1 complex with an actin monomer (Boquet et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

TetraThymosinβ Is Required for Actin Dynamics inCaenorhabditis elegansand Acts via Functionally Different Actin-binding Repeats

Troys

Ono

Dewitte

et al. 2004

MBoC

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Generating specific actin structures via controlled actin polymerization is a prerequisite for eukaryote development and reproduction. We here report on an essential Caenorhabditis elegans protein tetraThymosin␤ expressed in developing neurons and crucial during oocyte maturation in adults. TetraThymosin␤ has four repeats, each related to the actin monomer-sequestering protein thymosin␤4 and assists in actin filament elongation. For homologues with similar multirepeat structures, a profilin-like mechanism of ushering actin onto filament barbed ends, based on the formation of a 1:1 complex, is proposed to underlie this activity. We, however, demonstrate that tetraThymosin␤ binds multiple actin monomers via different repeats and in addition also interacts with filamentous actin. All repeats need to be functional for attaining full activity in various in vitro assays. The activities on actin are thus a direct consequence of the repeated structure. In containing both G-and F-actin interaction sites, tetraThymosin␤ may be reminiscent of nonhomologous multimodular actin regulatory proteins implicated in actin filament dynamics. A mutation that suppresses expression of tetraThymosin␤ is homozygous lethal. Mutant organisms develop into adults but display a dumpy phenotype and fail to reproduce as their oocytes lack essential actin structures. This strongly suggests that the activity of tetraThymosin␤ is of crucial importance at specific developmental stages requiring actin polymerization.

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Section: Introductionmentioning

confidence: 99%

TetraThymosinβ Is Required for Actin Dynamics inCaenorhabditis elegansand Acts via Functionally Different Actin-binding Repeats

Troys

Ono

Dewitte

et al. 2004

MBoC

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“…18,41 Both proteins bind actin monomers in a 1:1 complex with millimolar affinity and change between monomers on a time scale of seconds, but they have opposite effects on nucleotide exchange. thymosin b4 strongly inhibits exchange while profilin catalytically accelerates it over 100-fold (see Appendix Table A1).…”

Section: Mechanism Namementioning

confidence: 99%

“…44 One of the proteins modulating the intrinsic actin cycle is profilin, a monomer binding protein that catalyzes the rate exchange of ADP for ATP on monomeric actin 41,49 and then permits the assembly of its bound monomer at barbed but not pointed ends. 46 Because profilin quickly releases from barbed ends, it does not hinder further assembly.…”

Section: Introductionmentioning

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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“…Therefore, actin monomers can polymerize without other proteins, but the rate of formation of nucleation cores is too slow to account for the rapid changes in cell shapes that occur with reorganization of actin cytoskeleton. Furthermore, many G-actin sequestration factors, such as profilin and thymosins, are present in cells and sequester the majority of actin monomers present in cells [Pantoloni and Carlier, 1993]. Therefore, it is unlikely that nucleation cores are generated spontaneously from actin monomers under resting conditions, although formation of new actin cores is induced when cells are stimulated.…”

Section: Nucleation Core Formation: Critical Step For Initiation Of Amentioning

confidence: 99%

“…ADF/cofilin attacks the older ADP actin filaments that are likely to be at the tail end of an actin comet, promoting disassembly of the actin filaments [Carlier et al, 1997]. Profilin accelerates ADP/ATP exchange on actin monomers and thereby maintains the pool of ATP actin monomers available for polymerization [Pantoloni and Carlier, 1993]. Further, profilin accelerates N-WASP-Arp2/3 complex-mediated actin polymerization [Suetsugu et al, 1998;Yang et al, 2000].…”

Section: Simplified Model Of Actin Cytoskeleton Reorganization: Actinmentioning

confidence: 99%

Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2/3 complex and WASP/WAVE proteins

Suetsugu

Miki

Takenawa

2002

Cell Motil. Cytoskeleton

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How profilin promotes actin filament assembly in the presence of thymosin β4

Cited by 517 publications

References 36 publications

TetraThymosinβ Is Required for Actin Dynamics inCaenorhabditis elegansand Acts via Functionally Different Actin-binding Repeats

TetraThymosinβ Is Required for Actin Dynamics inCaenorhabditis elegansand Acts via Functionally Different Actin-binding Repeats

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2/3 complex and WASP/WAVE proteins

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