1. Processive flow by biased polymerization mediates the slow axonal transport of actin
- Author
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Christophe Leterrier, Nilaj Chakrabarty, Yong Tang, Archan Ganguly, Subhojit Roy, Peter Jung, Pankaj Dubey, Kelsey Ladt, Ohio University, University of Wisconsin-Madison, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, University of California [San Diego] (UC San Diego), University of California, Institut de neurophysiopathologie (INP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California (UC), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Population ,Models, Neurological ,Primary Cell Culture ,macromolecular substances ,Biology ,Axonal Transport ,Hippocampus ,Polymerization ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Microtubule ,Live cell imaging ,Slow axonal transport ,Report ,medicine ,Animals ,Computer Simulation ,Axon ,Cytoskeleton ,education ,Actin ,Research Articles ,030304 developmental biology ,Neurons ,0303 health sciences ,education.field_of_study ,Cell Biology ,Embryo, Mammalian ,Actins ,Rats ,medicine.anatomical_structure ,Animals, Newborn ,Axoplasmic transport ,Biophysics ,030217 neurology & neurosurgery - Abstract
Chakrabarty et al. propose a model in which slow axonal transport of actin can occur by a biased polymerization of actin filaments along the axon shaft without the involvement of microtubules (MTs) or MT-based motors. These dynamics are distinct from polymer sliding—the canonical mechanism thought to convey cytoskeletal cargoes in slow transport., 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.
- Published
- 2019