KIF3A IS A NEW MICROTUBULE-BASED ANTEROGRADE MOTOR IN THE NERVE AXON

Neurons are highly polarized cells composed of dendrites, cell bodies, and long axons. Because of the lack of protein synthesis machinery in axons, materials required in axons and synapses have to be transporte d down the axons after synthesis in the cell body. Fast anterograde tr ansport conveys different kinds of membranous organelles such as mitoc hondria and precursors of synaptic vesicles and axonal membranes, whil e organelles such as endosomes and autophagic prelysosomal organelles are conveyed retrogradely. Although kinesin and dynein have been ident ified as good candidates for microtubule-based anterograde and retrogr ade transporters, respectively, the existence of other motors for perf orming these complex axonal transports seems quite likely. Here we cha racterized a new member of the kinesin superfamily KIF3A (50-nm rod wi th globular head and tail), and found that it is localized in neurons, associated with membrane organelle fractions, and accumulates with an terogradely moving membrane organelles after ligation of peripheral ne rves. Furthermore, native KIF3A (a complex of 80/85 KIF3A heavy chain and a 95-kD polypeptide) revealed microtubule gliding activity and bac ulovirus-expressed KIF3A heavy chain demonstrated microtubule plus end -directed (anterograde) motility in vitro. These findings strongly sug gest that KIF3A is a new motor protein for the anterograde fast axonal transport.