What is slow axonal transport?

Abstract

While the phenomenon of slow axonal transport is widely agreed upon, its underlying mechanism has been controversial for decades. There is now persuasive evidence that several different mechanisms could contribute to slow axonal transport. Yet proponents of different theories have been hesitant to explicitly integrate what were, at least initially, opposing models. We suggest that slow transport is a multivariate phenomenon that arises through mechanisms that minimally include: molecular motor-based transport of polymers and soluble proteins as multi-protein complexes; diffusion; and en bloc transport of the axonal framework by low velocity transport and towed growth (due to increases in body size). In addition to integrating previously described mechanisms of transport, we further suggest that only a subset of transport modes operate in a given neuron depending on the region, length, species, cell type, and developmental stage. We believe that this multivariate approach to slow axonal transport better explains its complex phenomenology: including its bi-directionality; the differing velocities of transport depending on cargo, as well differing velocities due to anatomy, cell type and developmental stage.