Internexin,alpha-internexin, is a Class IVintermediate filament approximately66 kDa. The protein was originally purified from ratoptic nerve and spinal cord.^[1] The proteincopurifies with otherneurofilament subunits, as it was originally discovered, however in some mature neurons it can be the only neurofilament expressed. The protein is present in developingneuroblasts and in thecentral nervous system of adults. The protein is a major component of the intermediate filament network in smallinterneurons andcerebellar granule cells, where it is present in the parallel fibers.

Alpha-internexin has ahomologous centralrod domain of approximately 310amino acid residues that form a highly conservedalpha helical region. The central rod domain is responsible for coiled-coil structure and is flanked by anamino terminal head region and acarboxy terminal tail.^[2] This rod domain is also involved in the 10 nm filament assembly structure. The head and tail regions contain segments that are highly homologous to the NF-M’s structure.^[1] The head region is highly basic and contains manyserine andthreonine polymers while the tail region has distinct sequence motifs like a glutamate rich region.^[3] The alpha domain is composed ofheptad repeats ofhydrophobicresidues that aid the formation of acoiled coil structure.^[3] The structure of Alpha-internexin is highly conserved between rats, mice and humans.^[1]

Alpha-internexin can formhomopolymers, unlike theheteropolymer theneurofilaments form. This formation suggests that α-internexin and the three neurofilaments form separate filament systems.^[4] Not only can alpha-internexin form homopolymers but it form a network of extended filaments in the absence of other intermediate filament proteins and efficiently co-assemble with any type IV or type III subunit, in vitro.^[1] In Ching et al., a model of the intermediate filaments assembly is proposed. This model includes the following steps:

• Step 1: in the first step of IF assembly two parallel, unstaggeredintermediate filamentpolypeptides chains form adimer via theira-helical rod domains; these dimers can be eitherhomodimers orheterodimers.
• Step 2: the dimers may associate laterally to form antiparallel, unstaggeredtetramers or antiparallel, staggered tetramers.
• Step 3: the dimers may also associate longitudinally with a short head-to-tail overlap of the a-helical rod domains.
• Step 4: these lateral and longitudinal associations lead to the formation of protofibrils (octamers) and ultimately 10 nm intermediate filaments.^[5]

The close connection between the neurofilament triplet proteins and α-internexin is quite obvious. α-internexin is functionally interdependent with the neurofilament triplet proteins.^[4] If one genetically deletes NF-M and/or NF-H in mice, the transport and presence, in the axons of the Central Nervous System, of α-internexin will be drastically reduced. Not only are they functionally similar, the turnover rates are also similar among the four proteins.^[4]

It is expressed in early development in the neuroblast along with α-internexin andperipherin. As development continues into neurons theneurofilament triplet proteins (NF-L: neurofilament lowmolecular mass, NF-M: neurofilament medium molecular mass, and NF-H: neurofilament high molecular mass) are expressed in increasing molecular mass order as α-internexin expression decreases.^[3] In theneuroblast phase of development α-internexin is found in the neural tube and neural crest derived neuroblasts.

In adultcells, α-internexin is expressed abundantly in the centralnervous system, in thecytoplasm of neurons, along with the neurofilament triplet proteins. They are expressed in a relatively fixedstoichiometric ratio to neurofilaments.^[4]

Alpha-internexin is a brain and central nervous system filament that is involved inneuronal development and has been suggested to play a role inaxonal outgrowth. Gefiltin and xefiltin, homologs of α-internexin inzebrafish andXenopus laevis, respectively, are highly expressed duringretinal growth andoptic axon regeneration and therefore have aided the speculation that α-internexin and axonal outgrowth may be connected.^[1] With this speculation, studies have been performed to develop a stronger bridge between the two. Through knockout studies using mice, the inhibition of α-internexin had no visible effect on development of thenervous system which suggests that axonal outgrowth is unaffected by α-internexin, however, the knockout study failed to rule out subtle differences that the protein may have caused.^[4] Not only has α-internexin been linked to axonal outgrowth but it may regulate axonal stability or diameter through changes infilaments and theirsubunit composition.^[1] Also, internexin could be involved in the maintenance or the formation of dendritic spines.^[4] There have been many implications as to the function of α-internexin, but no concrete evidence currently exists to fully support or negate these speculations.

α-internexin has also been implicated in several degenerative diseases such asAlzheimer's disease,amyotrophic lateral sclerosis,dementia with Lewy bodies,Parkinson's disease,neuropathies,tropical spastic paraparesis(aHTLV-1 associatedmyelopathy). In HTLV-1 myelopathy,Tax,transactivator expressed by HTLV-1, interacts with α-internexin in cell culture resulting in dramatic reduction in Tax transcactivation and intermediate filament formation.

• Neurofilaments
• Intermediate filament

• Interactions of internexin alpha
• alpha-internexin at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 10

• Protein pages needing a picture