Neurofilaments are intrinsic determinants of axonal caliber

Neurofilaments (NFs) are intrinsic determinants of axonal caliber in large-caliber myelinated nerve fibers. Axonal caliber is influenced by the number of NFs in the axon (axonal NF content) and the spacing between adjacent NFs (interfilament distance). Axonal NF content depends on the level of NF gene expression, the amount of NF protein entering the axon, and the velocity at which NF protein moves within the axon. In this review we discuss possible factors affecting both axonal NF content and interfilament distance; these include the ratio of NF subunits, the level of phosphorylation of these subunits, interactions with target cells, and interactions with ensheathing glial cells.