The Role of Molecular Motors in Axonal Transport

Both cytoskeletal filaments and motor proteins are required for axonal transport. The cytoskeleton is a network of three types of protein filaments: microtubules, actin, and intermediate filaments. Structurally, molecular motors consist of two functional parts: a motor domain that interacts with cytoskeletal filaments and converts chemical energy into mechanical energy (energy from ATP hydrolysis is used for walking on the cytoskeletal filament); and a tail domain that interacts with cargo directly or through accessory chains or adaptors. Members of the kinesin superfamily and cytoplasmic dynein are the key motors in the axonal traffic machinery. Though both genetic and cellular studies have shown that kinesins are the primary motor for anterograde transport and dynein is the primary motor for retrograde transport, there is also clear evidence that the function of these motors in vivo is interdependent. Studies on axonal transport have shown that inhibition of either kinesin or dynein/dynactin results in a bidirectional block in transport, and genetic analysis has shown that mutations in kinesin, dynein, and dynactin show strong dominant genetic interactions. The motor proteins move a variety of cargos on microtubule tracks, including membrane organelles, protein complexes, complexes of nucleic acids, signaling molecules, and neuroprotective and repair molecules, and are required for the removal of misfolded or aggregated protein and vesicular and cytoskeleton components.