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bioRxiv · 10.1101/380113

Torsional stress generated by ADF/cofilin on cross-linked actin filaments boosts their severing

Wioland, H.·Jegou, A.·Romet-Lemonne, G.
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Abstract

Proteins of the Actin Depolymerizing Factor (ADF)/cofilin family are the central regulators of actin filament disassembly. A key function of ADF/cofilin is to sever actin filaments. However, how it does so in a physiological context, where filaments are interconnected and under mechanical stress, remains unclear. Here, we monitor and quantify the action of ADF/cofilin in different mechanical situations by using single molecule, single filament, and filament network techniques, coupled to microfluidics. We find that local curvature favors severing, while tension surprisingly has no effect on either cofilin binding or severing. Remarkably, we observe that filament segments that are held between two anchoring points, thereby constraining their twist, experience a mechanical torque upon cofilin binding. We find that this ADF/cofilin-induced torque does not hinder ADF/cofilin binding, but dramatically enhances severing. A simple model, which faithfully recapitulates our experimental observations, indicates that the ADF/cofilin-induced torque increases the severing rate constant 100-fold. A consequence of this mechanism, which we verify experimentally, is that cross-linked filament networks are severed by cofilin far more efficiently than non-connected filaments. We propose that this mechano-chemical mechanism is critical to boost ADF/cofilins ability to sever highly connected filament networks in cells.

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Wioland, H., Jegou, A., Romet-Lemonne, G.. 2018-07-31. Torsional stress generated by ADF/cofilin on cross-linked actin filaments boosts their severing. https://doi.org/10.1101/380113

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