PT  - JOURNAL ARTICLE
AU  - Nilaj Chakrabarty
AU  - Pankaj Dubey
AU  - Yong Tang
AU  - Archan Ganguly
AU  - Kelsey Ladt
AU  - Christophe Leterrier
AU  - Peter Jung
AU  - Subhojit Roy
TI  - Processive movement of Actin by Biased Polymerization: A new paradigm of Axonal Transport
AID  - 10.1101/212449
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 212449
4099  - http://biorxiv.org/content/early/2017/11/09/212449.short
4100  - http://biorxiv.org/content/early/2017/11/09/212449.full
AB  - 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/dis-assembly events (“hotspots”) and elongating polymers along the axon-shaft (“trails”). Using a combination of live imaging, super-resolution microscopy, and modeling, here we explore how these axonal actin dynamics can lead to processive transport. We found abundant actin nucleation, along with a 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 an anterogradely-biased flow of the population, at rates consistent with slow transport. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin. This mechanism is distinct from polymer-sliding, and seems well suited to convey highly dynamic cytoskeletal cargoes.Acknowledgements This work was supported by an NIH grant to SR (R01NS075233). The authors thank Stephanie Gupton (UNC) for the Mena/Vasp constructs.