Retrograde Axonal Transport: Applications in Trophic Factor Research

The extremely elongated processes of neurons—especially axons—present an unusual challenge to the metabolic machinery of the cell. A consequence of this geometry is that the metabolic and specialized (e.g., transmission) needs of axon terminals are dependent on the perikaryon (the primary biosynthetic site of the neuron) via shipment of the necessary material along the axon. This fundamental neuronal process is called “anterograde transport” and proceeds along at least five different rate classes, the highest of which (20–400 mm/d) constitute the fast anterograde transport and the lowest of which (0.1–20 mm/d) represent slow anterograde transport (Vallee and Bloom, 1991). An estimated fraction equivalent to 10–70% of fast anterograde transport is returned to the cell body via retrograde transport (Vallee and Bloom, 1991), with velocities ranging from 120 to 240 mm/ d (Schwab and Thoenen, 1980). Retrograde transport, much like fast anterograde transport, is blocked by microtubule assembly inhibitors such as colchicine and vinblastine (Grafstein and Forman, 1980), an effect that underlies an important role for microtubules in this biological process. The role of microtubules in retrograde transport has been clarified recently, with the discovery of the microtubule-associated motor proteins kinesin (responsible for anterograde transport) and MAP 1C (responsible for retrograde transport) (Vallee and Bloom, 1991).