Why slow axonal transport is bidirectional - can axonal transport of tau protein rely only on motor-driven anterograde transport?

Abstract

Slow axonal transport (SAT) moves multiple proteins from the soma, where they are synthesized, to the axon terminal. Due to the great lengths of axons, SAT almost exclusively relies on active transport, which is driven by molecular motors. The puzzling feature of slow axonal transport is its bidirectionality. Although the net direction of SAT is anterograde, from the soma to the terminal, experiments show that it also contains the retrograde component. One of the proteins transported by SAT is microtubule-associated protein tau. To better understand why the retrograde component in tau transport is needed, we used the perturbation technique. We analyzed the simplification of the full tau SAT model for the case when retrograde motor-driven transport and diffusion-driven transport of tau are negligible, and tau is driven only by anterograde (kinesin) motors. The solution of the simplified equations shows that the tau concentration along the axon length stays almost uniform (decreases very slightly), which is inconsistent with the tau concentration at the outlet boundary (at the axon tip). Thus kinesin-driven transport alone is not enough to explain the experimentally observed distribution of tau, and the retrograde motor-driven component in SAT is needed.