NEFM

NEFM, short for neurofilament medium polypeptide, is a gene that encodes the NF-M subunit of neurofilaments, a major component of the neuronal cytoskeleton. Neurofilaments are 10-nm intermediate filaments that provide structural support to axons and contribute to their diameter, which influences conduction velocity. NF-M co-polymerizes with the other neurofilament subunits, NF-L and NF-H, to form heteropolymers that assemble into mature neurofilaments in neurons of the central and peripheral nervous systems.

Protein structure and modification: Neurofilament medium polypeptide consists of an N-terminal head domain, a central coiled-coil rod domain, and a C-terminal tail domain. The tail is enriched in lysine-serine-proline (KSP) repeats, which are sites of extensive phosphorylation. This phosphorylation state modulates filament spacing, assembly, stability, and axonal transport.

Function and expression: NF-M participates in establishing and maintaining axonal caliber and contributes to the organization of the neuronal cytoskeleton. It is expressed in neurons throughout development and in mature nervous tissue, with particular abundance in long-projecting axons.

Regulation and clinical relevance: The assembly and function of neurofilaments, including NF-M, are regulated by phosphorylation and interactions with other cytoskeletal elements and motor proteins. Alterations in neurofilament expression or post-translational modification are observed in various neurodegenerative and neurodevelopmental conditions, and neurofilament proteins are commonly used as pathological markers in neurobiology research and diagnosis.

See also: neurofilament, NEFL, NEFH, neural cytoskeleton.