Local, biased polymerization kinetics lead to slow axonal transport of actin

Actin, a key protein constituent of the neuronal cytoskeleton is conveyed along the axon at rates corresponding to slow axonal transport. However, the mechanism of this movement is unknown. Recent advances in live imaging of F-actin and super-resolution imaging has revealed that axonal actin is highly dynamic, undergoing focal assembly, disassembly and elongation bidirectionally along the axon. Actin filaments have an anterograde bias, are locally polymerized and grow with their barbed ends attached to stationary axonal endosomes. We generated the dynamics of axonal actin trail assembly using a model of stochastic filament nucleation and elongation which incorporates imaging data. We then devised a photoactivation simulation to track fluorescently labeled actin in the axon, which closely matches the pulse-chase experiment paradigm. Our simulations predict that local, biased polymerization of actin trails lead to global, anterograde actin transport at rates matching in-vivo pulse-chase experimental rates. Collectively, the simulations and experiments point to local assembly and biased polymerization forming the mechanistic basis of bulk transport. This mechanism is distinct from motor-driven polymer sliding and occurs without any significant contribution from microtubules.