Critical roles for microtubules in axonal development and disease

Axons are occupied by dense arrays of cytoskeletal elements called microtubules, which are critical for generating and maintaining the architecture of the axon, and for acting as railways for the transport of organelles in both directions within the axon. Microtubules are organized and regulated by molecules that affect their assembly and disassembly, their stabilization, their association with other cytoskeletal elements, and their alignment and bundling with one another. Recent studies have accentuated the role of molecular motor proteins and microtubule-severing proteins in the establishment and maintenance of the axonal microtubule array. The growing body of knowledge on the proteins and mechanisms that regulate axonal microtubules has fostered a better understanding of how many debilitating diseases cause axons to degenerate. The purpose of this chapter is to provide an update on current knowledge of axonal microtubules and the proteins that regulate them, and to reflect on cutting-edge findings linking these proteins and mechanisms to diseases that afflict the human population.