Internexin, alpha-internexin, is a Class IV intermediate filament approximately 66

KDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...

. The protein was originally purified from rat optic nerve and spinal cord.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). The protein copurifies with other

neurofilament Neurofilaments (NF) 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 (~25 nm) and mi ...

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 and in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

of adults. The protein is a major component of the intermediate filament network in small

interneurons Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. I ...

and cerebellar granule cells, where it is present in the parallel fibers.

Structure

Alpha-internexin has a homologous central rod domain of approximately 310

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

residues that form a highly conserved alpha helical region. The central rod domain is responsible for coiled-coil structure and is flanked by an amino terminal head region and a carboxy terminal tail. 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. The head region is highly basic and contains many serine and threonine polymers while the tail region has distinct sequence motifs like a glutamate rich region.Catalogue# CPCA-a-Int: Chicken Polyclonal Antibody to alpha-internexin.
EnCor Biotechnology Inc. 2011. The alpha domain is composed of

heptad repeat The heptad repeat is an example of a structural motif that consists of a repeating pattern of seven amino acids: ''a b c d e f g'' H P P H C P C where H represents hydrophobic residues, C represents, typically, charged residues, and P repre ...

s of

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

s that aid the formation of a

coiled coil A coiled coil is a structural motif in proteins in which 2–7 alpha-helices are coiled together like the strands of a rope. (Dimers and trimers are the most common types.) Many coiled coil-type proteins are involved in important biological fu ...

structure. The structure of Alpha-internexin is highly conserved between rats, mice and humans. Microglia and neurons

Alpha-internexin can form homopolymers, unlike the heteropolymer the

neurofilaments Neurofilaments (NF) 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 (~25 nm) and mi ...

form. This formation suggests that α-internexin and the three neurofilaments form separate filament systems. 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. 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 polypeptides chains form a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ...

via their a-helical rod domains; these dimers can be either homodimers or heterodimers. *Step 2: the dimers may associate laterally to form antiparallel, unstaggered

tetramers A tetramer () (''tetra-'', "four" + ''-mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti(O ...

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.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. Journal of Cell Science. 112:2233-2240. (1999). The close connection between the neurofilament triplet proteins and α-internexin is quite obvious. α-internexin is functionally interdependent with the neurofilament triplet proteins.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). 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.

Function and expression

It is expressed in early development in the neuroblast along with α-internexin and

peripherin Peripherin is a type III intermediate filament protein expressed mainly in neurons of the peripheral nervous system. It is also found in neurons of the central nervous system that have projections toward peripheral structures, such as spinal motor ...

. As development continues into neurons the

triplet proteins (NF-L: neurofilament low

molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...

, 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. In the neuroblast phase of development α-internexin is found in the neural tube and neural crest derived neuroblasts. In adult cells, α-internexin is expressed abundantly in the central

nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...

, in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

of neurons, along with the neurofilament triplet proteins. They are expressed in a relatively fixed

stoichiometric Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions. Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equ ...

ratio to neurofilaments. Alpha-internexin is a brain and central nervous system filament that is involved in

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

al development and has been suggested to play a role in

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

al outgrowth. Gefiltin and xefiltin, homologs of α-internexin in

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ca ...

and

Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...

, respectively, are highly expressed during

retinal Retinal (also known as retinaldehyde) is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision). Some microorganisms use reti ...

growth and

optic Optics is the branch of physics that studies the behaviour and properties of light, including its interactions with matter and the construction of instruments that use or detect it. Optics usually describes the behaviour of visible, ultravio ...

axon regeneration and therefore have aided the speculation that α-internexin and axonal outgrowth may be connected. 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

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. Not only has α-internexin been linked to axonal outgrowth but it may regulate axonal stability or diameter through changes in filaments and their subunit composition. Also, internexin could be involved in the maintenance or the formation of dendritic spines. 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, amyotrophic lateral sclerosis,

dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time an ...

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

neuropathies Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...

tropical spastic paraparesis Tropical spastic paraparesis (TSP), is a medical condition that causes weakness, muscle spasms, and sensory disturbance by human T-lymphotropic virus resulting in paraparesis, weakness of the legs. As the name suggests, it is most common in tropic ...

and HTLV-1 associated myelopathy. 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.

References

External links

Interactions of internexin alpha
* {{Cytoskeletal Proteins

Structure

Function and expression

Disease associations

See also

References

External links