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Most axonal and synaptic proteins are synthesized within the cell body and must travel long distances along axons to reach their sites of function. It is widely accepted that membranous organelles are bidirectionally transported by motor proteins, including kinesins and dynein, at fast rates (50–400 mm/day) along axonal microtubules. The mechanisms underlying slow axonal transport of proteins, including components of the cytoskeleton, have been more elusive, although recent genetic and live-cell imaging approaches have yielded general principles about the dynamic behaviors of cytoskeletal elements and formation of the axonal cytoskeleton. Cytoskeletal components may undergo slow transport (0.1–10 mm/day in vivo) as short polymers or oligomeric assemblies of subunits that fully assemble during transport or after they incorporate into the axonal cytoskeleton. Slow transport rates for a particular cargo reflect a pattern of rapid movements along axons interrupted by pauses of varying short durations. In mature myelinated axons, proteins in transport represent a relatively small pool that serve as precursors to a large metabolically stable stationary cytoskeleton composed of neurofilaments networked together by cross bridging proteins along with microtubule and actin filaments. Cytoskeletal components may turn over by local subunit exchange or proteolysis or, alternatively, by detachment of a larger filament fragment that is translocated to a degradative site. Defects in specific aspects of this complex process are the basis for certain neurological disorders. [ABSTRACT FROM AUTHOR]

Because α-internexin is expressed in embryonic brain and can form homopolymers in vitro, it was originally considered to be an independent filament system critical mainly during brain development and distinct from that assembled in neurons from neurofilament (NF) triplet proteins. Analysis of mice engineered to eliminate individual or different combinations of NF triplet or α-internexin has proved that α-internexin and NF proteins are constituents of the same NF and functionally interdependent. α-Internexin satisfies all criteria previously used to establish the NF triplet proteins as subunits of a single intermediate filament and can now be considered to be a fourth subunit of NF in the adult CNS. Its role as a subunit of CNS NF explains the close relationship of α-internexin with the pathology of CNS diseases associated with NF accumulation. [ABSTRACT FROM AUTHOR]