| Stochastic severing of actin filaments by actin depolymerizing factor/cofilin controls the emergence of a steady dynamical regime. | |
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MedLine Citation:
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PMID: 18065447 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Actin dynamics (i.e., polymerization/depolymerization) powers a large number of cellular processes. However, a great deal remains to be learned to explain the rapid actin filament turnover observed in vivo. Here, we developed a minimal kinetic model that describes key details of actin filament dynamics in the presence of actin depolymerizing factor (ADF)/cofilin. We limited the molecular mechanism to 1), the spontaneous growth of filaments by polymerization of actin monomers, 2), the ageing of actin subunits in filaments, 3), the cooperative binding of ADF/cofilin to actin filament subunits, and 4), filament severing by ADF/cofilin. First, from numerical simulations and mathematical analysis, we found that the average filament length, L, is controlled by the concentration of actin monomers (power law: 5/6) and ADF/cofilin (power law: -2/3). We also showed that the average subunit residence time inside the filament, T, depends on the actin monomer (power law: -1/6) and ADF/cofilin (power law: -2/3) concentrations. In addition, filament length fluctuations are approximately 20% of the average filament length. Moreover, ADF/cofilin fragmentation while modulating filament length keeps filaments in a high molar ratio of ATP- or ADP-P(i) versus ADP-bound subunits. This latter property has a protective effect against a too high severing activity of ADF/cofilin. We propose that the activity of ADF/cofilin in vivo is under the control of an affinity gradient that builds up dynamically along growing actin filaments. Our analysis shows that ADF/cofilin regulation maintains actin filaments in a highly dynamical state compatible with the cytoskeleton dynamics observed in vivo. |
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Authors:
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Jeremy Roland; Julien Berro; Alphée Michelot; Laurent Blanchoin; Jean-Louis Martiel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-12-07 |
Journal Detail:
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Title: Biophysical journal Volume: 94 ISSN: 1542-0086 ISO Abbreviation: Biophys. J. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-28 Completed Date: 2008-05-22 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370626 Medline TA: Biophys J Country: United States |
Other Details:
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Languages: eng Pagination: 2082-94 Citation Subset: IM |
Affiliation:
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Université Joseph Fourier, TIMC-IMAG Laboratory, Grenoble, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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chemistry,
physiology* Adenosine Diphosphate / chemistry Adenosine Triphosphate / chemistry Cofilin 1 / chemistry* Computer Simulation Cytoskeleton / metabolism Destrin / chemistry* Kinetics Microfilaments / chemistry, metabolism* Models, Biological Models, Theoretical Stochastic Processes |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Cofilin 1; 0/Destrin; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate |
| Comments/Corrections | |
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