# Internexin

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> Source: https://en.wikipedia.org/wiki/Internexin
> Source revision: 1345363436
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{{Short description|Protein}}
{{infobox protein
| Name = Internexin neuronal intermediate filament protein, alpha
| caption = 
| image = 
| width = 
| HGNCid = 6057
| Symbol = INA
| AltSymbols = NEF5
| EntrezGene = 9118
| OMIM = 605338
| RefSeq = NM_032727
| UniProt = Q16352
| PDB = 
| ECnumber = 
| Chromosome = 10
| Arm = q
| Band = 24
| LocusSupplementaryData = 
}}
'''Internexin''', '''alpha-internexin''', is a Class IV [intermediate filament](/source/intermediate_filament) approximately {{val|66|ul=kDa}}. The protein was originally purified from rat [optic nerve](/source/optic_nerve) and spinal cord.<ref name=five>Levavasseur F, Zhu Q, and JP Julien. No requirement of alpha-internexin for nervous system development and for radial growth of axons. Molecular Brain Research. 69:104-112. (1999).</ref> The protein [copurifies](/source/copurification) with other [neurofilament](/source/neurofilament) subunits, as it was originally discovered, however in some mature neurons it can be the only neurofilament expressed. The protein is present in developing [neuroblasts](/source/neuroblasts) and in the [central nervous system](/source/central_nervous_system) of adults. The protein is a major component of the intermediate filament network in small [interneurons](/source/interneurons) and [cerebellar granule cell](/source/cerebellar_granule_cell)s, where it is present in the parallel fibers.

== Structure ==

Alpha-internexin has a [homologous](/source/Homology_(biology)) central [rod domain](/source/rod_domain) of approximately 310 [amino acid](/source/amino_acid) residues that form a highly conserved [alpha helical region](/source/Alpha_helix). The central rod domain is responsible for coiled-coil structure and is flanked by an [amino terminal](/source/amino_terminal) head region and a [carboxy terminal](/source/Carboxy-Terminal_Domain) tail.<ref>Lariviere, R. and JP Julien. Functions of Intermediate Filaments in Neuronal Development and Disease. Journal of Neurobiology. 58(1): 131-48. (2004).</ref> This rod domain is also involved in the 10&nbsp;nm filament assembly structure. The head and tail regions contain segments that are highly homologous to the NF-M's structure.<ref name=five/> The head region is highly basic and contains many [serine](/source/serine) and [threonine](/source/threonine) polymers while the tail region has distinct sequence motifs like a glutamate rich region.<ref name=two>[http://www.encorbio.com/cpolyclonal/CPCA-int.htm Catalogue# CPCA-a-Int: Chicken Polyclonal Antibody to alpha-internexin.] [EnCor Biotechnology Inc.](/source/EnCor_Biotechnology_Inc.) 2011.</ref> The alpha domain is composed of [heptad repeat](/source/heptad_repeat)s of [hydrophobic](/source/Hydrophobe) [residue](/source/residue_(chemistry))s that aid the formation of a [coiled coil](/source/coiled_coil) structure.<ref name=two/> The structure of Alpha-internexin is highly conserved between rats, mice and humans.<ref name=five/>

thumb|Mixed neuron/glial cultures from p18 rat embryo brain stained with antibody to alpha-internexin which reveals, in red, neuronal processes and cell bodies. Cells were also labelled in green for Coronin 1a, a marker for microglia.

Alpha-internexin can form [homopolymers](/source/Polymer), unlike the [heteropolymer](/source/heteropolymer) the [neurofilaments](/source/neurofilaments) form. This formation suggests that α-internexin and the three neurofilaments form separate filament systems.<ref name=four/> 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.<ref name=five/> 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, unstaggered [intermediate filament](/source/intermediate_filament) [polypeptide](/source/polypeptide)s chains form a [dimer](/source/protein_dimer) via their [a-helical](/source/Alpha_helix) rod domains; these dimers can be either [homodimers](/source/protein_dimer) or [heterodimer](/source/protein_dimer)s.
* '''Step 2''': the dimers may associate laterally to form antiparallel, unstaggered [tetramers](/source/tetrameric_protein) 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&nbsp;nm intermediate filaments.<ref>Ching G and R. Liem. Analysis of roles of the head domains of type IV rat neuronal intermediate filament proteins in filament assembly using domain-swapped [chimeric proteins](/source/Chimera_(protein)). Journal of Cell Science. 112:2233-2240. (1999).</ref>

The close connection between the neurofilament triplet proteins and α-internexin is quite obvious. α-internexin is functionally interdependent with the neurofilament triplet proteins.<ref name=four>Duprey, P and D. Paulin. What can be learned from intermediate filament gene regulation in the mouse embryo? International Journal of Developmental Biology. 39:443-457. (1995).</ref> 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.<ref name=four/>

== Function and expression ==

It is expressed in early development in the neuroblast along with α-internexin and [peripherin](/source/peripherin). As development continues into neurons the [neurofilament](/source/neurofilament) triplet proteins (NF-L: neurofilament low [molecular mass](/source/molecular_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.<ref name=two/> In the [neuroblast](/source/neuroblast) phase of development α-internexin is found in the neural tube and neural crest derived neuroblasts.

In adult [cells](/source/Cell_(biology)), α-internexin is expressed abundantly in the central [nervous system](/source/nervous_system), in the [cytoplasm](/source/cytoplasm) of neurons, along with the neurofilament triplet proteins. They are expressed in a relatively fixed [stoichiometric](/source/Stoichiometry) ratio to neurofilaments.<ref name=four/>

Alpha-internexin is a brain and central nervous system filament that is involved in [neuron](/source/neuron)al development and has been suggested to play a role in [axon](/source/axon)al outgrowth. Gefiltin and xefiltin, homologs of α-internexin in [zebrafish](/source/zebrafish) and [Xenopus laevis](/source/Xenopus_laevis), respectively, are highly expressed during [retinal](/source/retinal) growth and [optic](/source/optic) axon regeneration and therefore have aided the speculation that α-internexin and axonal outgrowth may be connected.<ref name=five/> 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 the [nervous system](/source/nervous_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.<ref name=four/> Not only has α-internexin been linked to axonal outgrowth but it may regulate axonal stability or diameter through changes in [filaments](/source/Protein_filament) and their [subunit](/source/Protein_subunit) composition.<ref name=five/> Also, internexin could be involved in the maintenance or the formation of dendritic spines.<ref name=four/> 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.

== Disease associations ==

α-internexin has also been implicated in several degenerative diseases such as [Alzheimer's disease](/source/Alzheimer's_disease), [amyotrophic lateral sclerosis](/source/amyotrophic_lateral_sclerosis), [dementia with Lewy bodies](/source/dementia_with_Lewy_bodies), [Parkinson's disease](/source/Parkinson's_disease), [neuropathies](/source/neuropathies), [tropical spastic paraparesis](/source/tropical_spastic_paraparesis)(a [HTLV-1](/source/HTLV-1) associated [myelopathy](/source/myelopathy)). In HTLV-1 myelopathy, [Tax](/source/Primate_T-lymphotropic_virus), [transactivator](/source/transactivator) expressed by HTLV-1, interacts with α-internexin in cell culture resulting in dramatic reduction in Tax transcactivation and intermediate filament formation.

== See also ==
* [Neurofilaments](/source/Neurofilaments)
* [Intermediate filament](/source/Intermediate_filament)

== References ==
{{reflist}}

== External links ==
* [http://www.ihop-net.org/UniPub/iHOP/gs/320717.html Interactions of internexin alpha]
* {{MeshName|alpha-internexin}}

{{Cytoskeletal Proteins}}

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Adapted from the Wikipedia article [Internexin](https://en.wikipedia.org/wiki/Internexin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Internexin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.