Slow axonal transport of neurofilaments and axon caliber
Brain function relies on the correct timing of the arrival of the electric signals at neurons and hence the correct speed at which they travel along neuronal axons. The speed of the electric signal depends strongly on the diameter of the axon, which therefore must be precisely matched to its physiologic function.
The principal determinant of axon diameter in vertebrates are space-filling cytoskeletal polymers called neurofilaments. Morphometric studies have indeed established a direct correlation between the abundance of neurofilaments and axonal diameter. In addition to their space-filling role, neurofilaments are also cargo of slow axonal transport. They are assembled in the cell body and transported by microtubule based molecular motors toward the nerve terminals. The focus of our collaborative research with the Brown-lab at Ohio State University is a new model for the formation of axon caliber that is rooted in the dual motile and architectural function of neurofilaments and the distribution of microtubule tracks in the axonal cytoskeleton. According to this view, axon caliber is emergent and dynamically determined by changes in the flow of neurofilaments. I will discuss specific predictions of this new model and how they are supported experimentally. We hope that this study will provide insights into the mechanisms of axonal swelling associated with a number of neurodegenerative diseases.