title: Actin-filament stochastic dynamics mediated by ADF/cofilin.
abstract: BACKGROUND
  The rapid dynamics of actin filaments is a fundamental process that powers a large number of cellular functions. However, the basic mechanisms that control and coordinate such dynamics remain a central question in cell biology. To reach beyond simply defining the inventory of molecules that control actin dynamics and to understand how these proteins act synergistically to modulate filament turnover, we combined evanescent-wave microscopy with a biomimetic system and followed the behavior of single actin filaments in the presence of a physiologically relevant mixture of accessory proteins. This approach allows for the real-time visualization of actin polymerization and age-dependent filament severing.
  
  
  RESULTS
  In the presence of actin-depolymerizing factor (ADF)/cofilin and profilin, actin filaments with a processive formin attached at their barbed ends were observed to oscillate between stochastic growth and shrinkage phases. Fragmentation of continuously growing actin filaments by ADF/cofilin is the key mechanism modulating the prominent and frequent shortening events. The net effect of continuous actin polymerization, driven by a processive formin that uses profilin-actin, and of ADF/cofilin-mediating severing that trims the aged ends of the growing filaments is an up to 155-fold increase in the rate of actin-filament turnover in vitro in comparison to that of actin alone. Lateral contact between actin filaments dampens the dynamics and favors actin-cable formation. A kinetic simulation accurately validates these observations.
  
  
  CONCLUSIONS
  Our proposed mechanism for the control of actin dynamics is dominated by ADF/cofilin-mediated filament severing that induces a stochastic behavior upon individual actin filaments. When combined with a selection process that stabilizes filaments in bundles, this mechanism could account for the emergence and extension of actin-based structures in cells.
authors.affiliation: Institut de Recherches en Technologie et Sciences pour le Vivant, Laboratoire de Physiologie Cellulaire Végétale, CEA Grenoble, Université Joseph Fourier, 17 rue des Martyrs, F38054 Grenoble, France.
authors.forename: Alphée
authors.initials: A
authors.lastname: Michelot
authors.forename: Julien
authors.initials: J
authors.lastname: Berro
authors.forename: Christophe
authors.initials: C
authors.lastname: Guérin
authors.forename: Rajaa
authors.initials: R
authors.lastname: Boujemaa-Paterski
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Staiger
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Martiel
authors.forename: Laurent
authors.initials: L
authors.lastname: Blanchoin
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000502:physiology*; D032701:Biomimetics / Q000379:methods; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D013269:Stochastic Processes
chemical_list: D051339:Actin Depolymerizing Factors