page_title: Neurofilament
section_title: Neurofilament assembly and structure
hierarchical_section_title: Neurofilament / Neurofilament assembly and structure
caption_attribution_description: English: Cortical neuron stained with antibody to neurofilament subunit NF-L in green. In red are neuronal stem cells stained with antibody to alpha-internexin. Image created using antibodies from EnCor Biotechnology Inc.
context_page_description: Neurofilaments are classed as type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with microtubules and microfilaments, they form the neuronal cytoskeleton. They are believed to function primarily to provide structural support for axons and to regulate axon diameter, which influences nerve conduction velocity. The proteins that form neurofilaments are members of the intermediate filament protein family, which is divided into six types based on their gene organization and protein structure. Types I and II are the keratins which are expressed in epithelia. Type III contains the proteins vimentin, desmin, peripherin and glial fibrillary acidic protein. Type IV consists of the neurofilament proteins L, M, H and internexin. Type V consists of the nuclear lamins, and type VI consists of the protein nestin. The type IV intermediate filament genes all share two unique introns not found in other intermediate filament gene sequences, suggesting a common evolutionary origin from one primitive type IV gene.
context_section_description: Like other intermediate filament proteins, the neurofilament proteins all share a common central alpha helical region, known as the rod domain because of its rod-like tertiary structure, flanked by amino terminal and carboxy terminal domains that are largely unstructured.  The rod domains of two neurofilament proteins dimerize to form an alpha-helical coiled coil.  Two dimers associate in a staggered antiparallel manner to form a tetramer.  This tetramer is believed to be the basic subunit (i.e. building block) of the neurofilament.  Tetramer subunits associate side-to-side to form unit-length filaments, which then anneal end-to-end to form the mature neurofilament polymer, but the precise organization of these subunits within the polymer is not known, largely because of the heterogeneous protein composition and the inability to crystallize neurofilaments or neurofilament proteins.  Structural models generally assume eight tetramers (32 neurofilament polypeptides) in a filament cross-section, but measurements of linear mass density suggest that this can vary.
  
  The amino terminal domains of the neurofilament proteins contain numerous phosphorylation sites and appear to be important for subunit interactions during filament assembly.  The carboxy terminal domains appear to be intrinsically disordered domains that lack alpha helix or beta sheet.  The different sizes of the neurofilament proteins 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.
caption: Rat brain cells grown in tissue culture and stained, in green, with an antibody to neurofilament subunit NF-L, which reveals a large neuron. The culture was stained in red for alpha-internexin, which in this culture is found in neuronal stem cells surrounding the large neuron. Image courtesy of EnCor Biotechnology Inc.
exif: {"Image Software": "Picasa 3.0", "Image ExifOffset": "50", "Thumbnail Compression": "JPEG (old-style)", "Thumbnail XResolution": "72", "Thumbnail YResolution": "72", "Thumbnail ResolutionUnit": "Pixels/Inch", "Thumbnail JPEGInterchangeFormat": "288", "Thumbnail JPEGInterchangeFormatLength": "7918", "EXIF ExifVersion": "0210", "EXIF DateTimeOriginal": "2000:02:04 05:00:00", "Interoperability InteroperabilityIndex": "", "Interoperability InteroperabilityVersion": "[48, 49, 48, 48]", "EXIF InteroperabilityOffset": "158", "EXIF ImageUniqueID": "e8cb2179e2d1819f5242c71428451805"}