ntracellular transport is carried out by three sets of molecular motors: myosins, kinesins and dyneins. Myosins move on microfilaments and are thought to be responsible for short range transport, whereas kinesin and dynein proteins use microtubules as tracks for long distance transport and are capable of recognizing the microtubule polarity (36). A number of studies have shown that most kinesin-family motors move towards the plus-end of the microtubules that are usually used to deliver cargos towards the synapse. On the contrary, dynein moves in the opposite direction for transport toward the cell body (37). Kinesins and dyneins have “motor domains” that travel along the microtubules in a distinct direction by using the energy resultant from ATP hydrolysis.

Kinesins are microtubule based anterograde intracellular transport motors (Figure 1). Newly synthesized components at cell body indispensable for neuronal function and maintenance are transported anterogradely from the soma to nerve terminals. Ultrastructural studies have demonstrated many small vesicles, tubulo-vesicular structures, mitochondria and dense-core vesicles move along the axon by fast anterograde transport (38). Components transported in fast anterograde transport are required not only for the supply and turnover of intracellular membrane compartments such as mitochondria, but also for the transport of proteins required for the maintenance of axonal metabolism (3). Conventional kinesins usually form a protein dimer of two identical heavy chains and each of them binds to a kinesin light chain. The heavy chain contains a highly conserved globular head called motor domain, which includes a microtubule-binding site and an ATP-binding/hydrolysis site, a short, flexible neck linker, a stalk domain, which has a long, central coiled-coil region for dimerization and a tail domain for light chain and cargo binding (39). Kinesin move in a hand-over-hand mechanism over long distances along the microtubuleprior to detaching, allowing a very efficient cargo transport (40).

In opposition to anterograde axonal transport, which can be carried out by several different kinesin motor proteins, cytoplasmic dynein is the major motor protein responsible retrograde transport (Figure 1). Cytoplasmic dynein is a multi-subunit complex containing light chains, light intermediate chains and two heavy chains that bind microtubules. The heavy chains contain ATPase activity and are therefore responsible for generating movement along the axon microtubules, while the other chains are involved in cargo binding and binding to dynactin (41). The overall motility tendency is pointed toward microtubule minus end, but the ability of dynein to change directions may allow it to contour obstacles encountered along the axon during transport. Studies on dynein demonstrate that this motor protein wanders along the microtubule, and frequentl