The mechanism and regulation of fast axonal transport

Recent in vitro studies of microtubule-dependent organelle movement have provided a great deal of information on the molecular mechanism of fast axonal transport. Microtubule-dependent organelle movement occurs in most cells¹, but in neurons active transport is absolutely necessary for materials to travel from the cell body to the synapse. Since fast transport is crucial for neuronal survival, it is likely that specialized regulatory mechanisms have been developed. It is clear that the microtubule-based motors, kinesin and cytoplasmic dynein are the enzymes that power organelle motility; however, additional cytoplasmic components are required to create an 'organelle translocation complex' that is competent for transport. Organelle transport might be regulated at the level of any of these components, i.e. the motors, their accessory factors, or the organelle binding sites. The direction of organelle movement is probably governed by the membrane binding site. In this review we discuss these topics and consider the mechanism of transport of the retrograde motor, cytoplasmic dynein, to the nerve terminal, and possible ways that unidirectional transport could occur on the non-polarized array of microtubules found in some dendrites.