Processive flow by biased polymerization mediates the slow axonal transport of actin

Abstract : Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/disassembly events ("actin hotspots") and elongating polymers along the axon shaft ("actin trails"). Using a combination of live imaging, superresolution microscopy, and modeling, in this study, we explore how these dynamic structures can lead to processive transport of actin. We found relatively more actin trails elongated anterogradely as well as an overall slow, anterogradely biased flow of actin in axon shafts. Starting with first principles of monomer/filament assembly and incorporating imaging data, we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to a slow anterogradely biased flow of the population. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin without involvement of microtubules (MTs) or MT-based motors. Mechanistically distinct from polymer sliding, this might be a general strategy to convey highly dynamic cytoskeletal cargoes.
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Nilaj Chakrabarty, Pankaj Dubey, Yong Tang, Archan Ganguly, Kelsey Ladt, et al.. Processive flow by biased polymerization mediates the slow axonal transport of actin. Journal of Cell Biology, Rockefeller University Press, 2019, 218 (1), pp.112-124. ⟨10.1083/jcb.201711022⟩. ⟨hal-02073336⟩

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