are largely due to differences in the length of the carboxy terminal domains. These domains are rich in acidic and basic amino acid residues. The carboxy terminal domains of NFM and NFH are the longest and are modified extensively by post-translational modifications such as phosphorylation and glycosylation in vivo. They project radially from the filament backbone to form a dense brush border of highly charged and unstructured domains analogous to the bristles on a bottle brush. These entropically flailing domains have been proposed to define a zone of exclusion around each filament, effectively spacing the filaments apart from their neighbors. In this way, the carboxy terminal projections maximize the space-filling properties of the neurofilament polymers. By electron microscopy, these domains appear as projections called sidearms that appear to contact neighboring filaments. Neurofilament function Neurofilaments are found in vertebrate neurons in especially high concentrations in axons, where they are all aligned in parallel along the long axis of the axon forming a continuously overlapping array. They have been proposed to function as space-filling structures that increase axonal diameter. Their contribution to axon diameter is determined by the number of neurofilaments in the axon and their packing density. The number of neurofilaments in the axon is thought to be determined by neurofilament gene expression and axonal transport. The packing density of the filaments is determined by their side-arms which define the spacing between neighboring filaments. Phosphorylation of the sidearms is thought to increase their extensibility, increasing the spacing between neighboring filaments by the binding of divalent cations between the sidearms of adjacent filaments Early in development, axons are narrow processes that contain relatively few neurofilaments. Those axons that become myelinated accumulate more neurofilaments, which drives the expansion of their caliber. After an axon has grown and connected with its target cell, the diameter of the axon may increase as much as fivefold. This is caused by an increase in the number of neurofilaments exported from the nerve cell body as well as a slowing of their rate of transport. In mature myelinated axons, neurofilaments can be the single most abundant cytoplasmic structure and can occupy most of the axonal cross-sectional area. For example, a large myelinated axon may contain thousands of neurofilaments in one cross-section Neurofilament transport In addition to their structural role in axons, neurofilaments are also cargoes of axonal transport. Most of the neurofilament proteins in axons are synthesized in