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Alphée Michelot

Stochastic dynamics of actin filaments. From single molecule to organized actin filaments based structures

Published on 6 July 2007

Thesis presented July 06, 2007

Actin is one of the major constituents of the cytoskeleton. By dynamically assembling in cells, actin filaments are able to push the membrane out, and deform the cell leading to force generation and movement. In the last ten years, biochemical studies have unveiled many different biochemical pathways that lead to actin polymerization and assembly. However, the mechanism of force generation is still under debate. The main issue is how the microscopic properties of individual filaments are integrated at the scale of a cell to produce forces. In addition, little is known about the dynamic formation and disassembly of actin filaments cables (an organization​ of actin filaments in parallel/or antiparallel bundles). Recently, formins have been shown to be an essential family of proteins for the initiation of such actin-based structures.
This manuscript highlights the work that we conduct to understand the mechanism of action of formins at a molecular level. Most of formins are processive nucleators; indeed they are promoting fast actin filament elongation while remaining attached to the growing end of the filament. We have shown by the original evanescent wave microscopy technique that Arabidopsis thaliana FORMIN1 represents a new kind of formin, which moves to the side of the actin filament after nucleation. From the side of the pre-existing filament, FORMIN1 is able to nucleate a new filament, promoting the assembly of actin filaments into actin cables. We next combine biomimetic assays with TIRF microscopy, to address the mechanism of the dynamic of polymerization and depolymerization​ of actin filaments induced by ADF/cofilin. We visualized for the first time individual actin filament stochastic dynamics in real time, and proposed a selection process for the formation of large actin based structures initiated by formin.

Actin, cytoskeleton, formins, cables, filaments, ADF/cofilin, stochastic dynamics, forces, processivity, microscopy, evanescent wave, motility, symmetry breaking

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