The axonal cytoskeleton. Courtesy of N. Hirokawa, University of Tokyo, Japan.

The field of slow axonal transport is divided between those who believe that cytoskeletal subunits are transported along the axon (the subunit model) and those who believe that entire filaments move (the polymer model). What both camps have in common is ignorance of the precise transport mechanism, whatever the cargo might be. Reporting in Cell, Hirokawa and colleagues now provide evidence that slow axonal movement requires kinesin motors and microtubule tracks.

The visualization of slow axonal transport is not trivial (see Anthony Brown's article on page 153 of this issue), and finding an appropriate model system is half the job. Hirokawa and colleagues used the squid giant axon in their studies because it has two advantages: it is translucent and it is big. They injected fluorescent tubulin into the axon and measured the speed at which it moved away from the cell body. The values obtained with this experimental set-up were similar to those reported for mammalian axons.

In a series of pharmacological studies, the speed of movement was considerably reduced when microtubules were depolymerized, but remained constant in the absence of polymerized actin microfilaments. Similarly, transport was slowed down when kinesin's motor activity was inhibited, but myosin seemed to be dispensable for this process.

Hirokawa and colleagues also observed that the diffusion rate of the transported tubulin is lower than the diffusion rate of creatine kinase (another cargo for slow axonal transport), but higher than the diffusion rate of taxol-stabilized microtubules. The authors interpret this finding as an indication that tubulin is transported in a complex that is large but different from a fully polymerized microtubule. This would tilt the balance in favour of the subunit model again, at least for the transport of tubulin. Figuring out the polymerization state of tubulin transported in this complex will hopefully clarify this issue.