Neurofilament dynamics: a tug of war by microtubule motors

Structural support for axons, which can consist of volumes thousands of times larger than the neuronal perikaryon, is provided in part by neurofilaments (NFs), the major fibrous constituent of the axonal cytoskeleton. Most NFs undergo anterograde transport (towards the synapse or growth cone), while a few undergo retrograde transport (back towards the perikaryon). Some NFs exhibit an extended residence time along axons, which allows NFs to provide structural support to the axon yet minimizes NF turnover, which would otherwise impart a prohibitive metabolic burden upon the neuron. Herein, we explore known and hypothesized roles for microtubule motors in transport and distribution of NFs along axons. We present evidence that those NFs that display extended residence along axons are critically dependent upon surrounding microtubules, and that simultaneous interaction with multiple microtubule motors provides the architectural force regulating their distribution.