Intermittent depolymerization of actin filaments is caused by photo-induced dimerization of actin protomers

Abstract : Actin, one of the most abundant proteins within eukaryotic cells, assembles into long filaments that form intricate cytoskeletal networks and are continuously remodelled via cycles of actin polymer-ization and depolymerization. These cycles are driven by ATP hy-drolysis, a process that also acts to destabilize the filaments as they grow older. Recently, abrupt dynamical changes during the depo-lymerization of single filaments have been observed and seemed to imply that old filaments are more stable than young ones [Kueh HY, et al. (2008) Proc Natl Acad Sci USA 105:16531-16536]. Using improved experimental setups and quantitative theoretical analysis , we show that these abrupt changes represent actual pauses in depolymerization, unexpectedly caused by the photo-induced formation of actin dimers within the filaments. The stochastic dimerization process is triggered by random transitions of single, fluorescently labeled protomers. Each pause represents the delayed dissociation of a single actin dimer, and the statistics of these single molecule events can be determined by optical microscopy. Unlabeled actin filaments do not exhibit pauses in depolymeriza-tion, which implies that, in vivo, older filaments become destabilized by ATP hydrolysis, unless this aging effect is overcompensated by actin-binding proteins. The latter antagonism can now be systematically studied for single filaments using our combined experimental and theoretical method. Furthermore, the dimerization process discovered here provides a molecular switch, by which one can control the length of actin filaments via changes in illumination. This process could also be used to locally "freeze" the dynamics within networks of filaments.
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Contributor : Emmanuèle Helfer <>
Submitted on : Thursday, January 10, 2019 - 3:01:28 PM
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Thomas Niedermayer, Antoine Jégou, Lionel Chièze, Bérengère Guichard, Emmanuèle Helfer, et al.. Intermittent depolymerization of actin filaments is caused by photo-induced dimerization of actin protomers. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2012, 109 (27), pp.10769-10774. ⟨10.1073/pnas.1121381109⟩. ⟨hal-01961001⟩



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