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Global treadmilling coordinates actin turnover and controls the size of actin networks

Abstract

Various cellular processes (including cell motility) are driven by the regulated, polarized assembly of actin filaments into distinct force-producing arrays of defined size and architecture. Branched, linear, contractile and cytosolic arrays coexist in vivo, and cells intricately control the number, length and assembly rate of filaments in these arrays. Recent in vitro and in vivo studies have revealed novel molecular mechanisms that regulate the number of filament barbed and pointed ends and their respective assembly and disassembly rates, thus defining classes of dynamically different filaments, which coexist in the same cell. We propose that a global treadmilling process, in which a steady-state amount of polymerizable actin monomers is established by the dynamics of each network, is responsible for defining the size and turnover of coexisting actin networks. Furthermore, signal-induced changes in the partitioning of actin to distinct arrays (mediated by RHO GTPases) result in the establishment of various steady-state concentrations of polymerizable monomers, thereby globally influencing the growth rate of actin filaments.

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Figure 1: Actin assembly workshops in cells.
Figure 2: The role of ADF/cofilin in the regulation of treadmilling of actin filaments.
Figure 3: A global treadmilling model accounts for the functional <>balance between various actin networks in motile processes.

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Acknowledgements

This work was supported by a European Research Council (ERC) advanced grant 'Forcefulactin' number 249982 to M.-F.C. The authors thank B. Avvaru and S. Kuhn for help with structural drawings. The authors thank J. Pernier and A. Lomakin for helpful discussions, and J. Lippincott-Schwartz, L. Machesky and K. Rottner for critical reading of the manuscript.

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Targeting of actin barbed ends by actin regulators. (PDF 515 kb)

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Molecular mechanism of filament branching by WASP-Arp2/3 complex: possible models and role of the WH2 domain of WASP proteins (PDF 196 kb)

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Carlier, MF., Shekhar, S. Global treadmilling coordinates actin turnover and controls the size of actin networks. Nat Rev Mol Cell Biol 18, 389–401 (2017). https://doi.org/10.1038/nrm.2016.172

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