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Curr Biol. 2017 Jul 10;27(13):1956-1967.e7. doi: 10.1016/j.cub.2017.05.048. Epub 2017 Jun 15.

ADF/Cofilin Accelerates Actin Dynamics by Severing Filaments and Promoting Their Depolymerization at Both Ends.

Author information

1
Institut Jacques Monod, CNRS, Université Paris Diderot, 75013 Paris, France.
2
Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
3
Institut Jacques Monod, CNRS, Université Paris Diderot, 75013 Paris, France. Electronic address: antoine.jegou@ijm.fr.
4
Institut Jacques Monod, CNRS, Université Paris Diderot, 75013 Paris, France. Electronic address: romet@ijm.fr.

Abstract

Actin-depolymerizing factor (ADF)/cofilins contribute to cytoskeletal dynamics by promoting rapid actin filament disassembly. In the classical view, ADF/cofilin sever filaments, and capping proteins block filament barbed ends whereas pointed ends depolymerize, at a rate that is still debated. Here, by monitoring the activity of the three mammalian ADF/cofilin isoforms on individual skeletal muscle and cytoplasmic actin filaments, we directly quantify the reactions underpinning filament severing and depolymerization from both ends. We find that, in the absence of monomeric actin, soluble ADF/cofilin can associate with bare filament barbed ends to accelerate their depolymerization. Compared to bare filaments, ADF/cofilin-saturated filaments depolymerize faster from their pointed ends and slower from their barbed ends, resulting in similar depolymerization rates at both ends. This effect is isoform specific because depolymerization is faster for ADF- than for cofilin-saturated filaments. We also show that, unexpectedly, ADF/cofilin-saturated filaments qualitatively differ from bare filaments: their barbed ends are very difficult to cap or elongate, and consequently undergo depolymerization even in the presence of capping protein and actin monomers. Such depolymerizing ADF/cofilin-decorated barbed ends are produced during 17% of severing events. They are also the dominant fate of filament barbed ends in the presence of capping protein, because capping allows growing ADF/cofilin domains to reach the barbed ends, thereby promoting their uncapping and subsequent depolymerization. Our experiments thus reveal how ADF/cofilin, together with capping protein, control the dynamics of actin filament barbed and pointed ends. Strikingly, our results propose that significant barbed-end depolymerization may take place in cells.

KEYWORDS:

actin dynamics; actin-depolymerizing factor; barbed-end depolymerization; capping protein; cofilin; microfluidics; non-muscle actin; single filaments

PMID:
28625781
PMCID:
PMC5505867
DOI:
10.1016/j.cub.2017.05.048
[Indexed for MEDLINE]
Free PMC Article

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