Stochastic severing of actin filaments by actin depolymerizing factor/cofilin controls the emergence of a steady dynamical regime

Biophys J. 2008 Mar 15;94(6):2082-94. doi: 10.1529/biophysj.107.121988. Epub 2007 Dec 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism*
  • Actins / chemistry
  • Actins / physiology*
  • Adenosine Diphosphate / chemistry
  • Adenosine Triphosphate / chemistry
  • Cofilin 1 / chemistry*
  • Computer Simulation
  • Cytoskeleton / metabolism
  • Destrin / chemistry*
  • Kinetics
  • Models, Biological
  • Models, Theoretical
  • Stochastic Processes

Substances

  • Actins
  • Cofilin 1
  • Destrin
  • Adenosine Diphosphate
  • Adenosine Triphosphate