Disease relevance of Ina

• After P5, alpha-internexin is found to colocalize with other neuronal intermediate filaments in the cell processes of horizontal and ganglion cells, but its expression is barely detectable in amacrine cells processes [1].
• Neuronal intermediate filament protein alpha-internexin facilitates axonal neurite elongation in neuroblastoma cells [2].
• The results strongly support the view that alpha-internexin is a fourth subunit of neurofilaments in the adult CNS, providing a basis for its close relationship with neurofilaments in CNS diseases associated with neurofilament accumulation [3].
• The involvement of neurofilaments in disease is supported by the discovery of novel mutations in the neurofilament heavy gene from cases of amyotrophic lateral sclerosis and by reports of neuronal death in mouse models expressing neurofilament and alpha-internexin transgenes [4].
• Alpha-internexin as a corneal autoantigen in spontaneous autoimmune keratitis mouse model [5].

High impact information on Ina

• Three currents were studied: a rapid tetrodotoxin-sensitive Na+ current (Ina), an early outward K+ current sensitive to 4-aminopyridine (IA), and an inward current activated by the excitatory amino acid receptor agonist kainate [6].
• This Mr 60,000 protein, which we designate A60, is distinct from other known neurofilament-associated proteins, including the Mr 60,000 protein alpha-internexin and the Mr 58,000 intermediate filament protein peripherin [7].
• Immunocytochemical assay of cultured DRG neurons from dt embryos revealed that alpha-internexin was aggregated in the proximal region of axons and juxtanuclear region of the cytoplasma, yet the other intermediate filament proteins were widely distributed in all processes [8].
• We found that not only BPAG1, but also alpha-internexin was absent in the DRG neurons in adult dt mice [8].
• RESULTS: Immunoblot analysis revealed alpha-internexin to be the target antigen of OT-20 that specifically recognizes corneal epithelium [5].

Biological context of Ina

• Unexpectedly, alpha-internexin -/- mice developed normally and did not exhibit overt phenotypes [9].
• Comparison of the mouse, rat and human NF-66 indicated > 90% homology in protein sequence and 85% homology in coding nucleotide sequence [10].
• Poly-ADP-ribosylated peptides identified using a proteomics approach yielded several proteins potentially associated with memory, including structural proteins (tubulin alpha and beta, gamma-actin, and alpha-internexin neuronal intermediate filament protein) and 14-3-3gamma [11].
• After introducing DNA constructs into non-neuronal 3T3 fibroblasts and a neuronal Neuro2A cell line by lipofectamine transfection, we observed that the expression of EGFP with 1.3 kb mouse alpha-internexin promoter was in a neuron-dominant manner [12].

Anatomical context of Ina

• The neuronal intermediate filament, alpha-internexin is transiently expressed in amacrine cells in the developing mouse retina [1].
• The transient presence of alpha-internexin in amacrine cells only in early development suggests that the protein may play a role in the plasticity of neuronal connections in the retina [1].
• Moreover, the absence of alpha-internexin did not interfere with neurite extension of cultured DRG neurons [9].
• The number and caliber of L4 ventral root axons remained unchanged in alpha-internexin -/- mice [9].
• In the retina, alpha-internexin begins to be expressed in retinal ganglion cells when their first axons reach the optic chiasma [9].

Enzymatic interactions of Ina

• Under these conditions, however, NF-M transport is completely abolished by deleting alpha-internexin [13].

Other interactions of Ina

• Some small neurons in the adult olfactory bulb were uniquely labeled with antibody to alpha-internexin [14].
• No intermediate filament structures were detectable in optic nerve of alpha-internexin -/-; NF-L -/- mice [9].
• Microscopic analysis revealed no gross morphological defects in the ventral and dorsal roots, spinal cord, retina and gut, but protein analyses showed increased levels of the type IV IF alpha-internexin in ventral roots of peripherin null mice [15].
• A polyclonal antiserum raised specifically to NF-66 and unreactive to NF-L, -M, -H, and peripherin was used for immunocytochemical staining [16].
• The Ina antigen is affected by papain, trypsin, bromelin and neuraminidase [17].

Analytical, diagnostic and therapeutic context of Ina

• Electron microscopy did not reveal significant differences in axonal calibers, in myelination of axons and in neurofilament structures between alpha-internexin -/- and control mice during development and at adult stage [9].
• This in vitro observation is consistent with results from immunocytochemistry and in situ hybridization studies of developing granule neurons in vivo, which suggest that alpha-internexin is the major neuronal intermediate filament protein in developing granule neurons [18].
• The 66-kDa neurofilament protein (NF-66): sequence analysis and evolution [10].
• Therefore, the cre transgene driven by mouse alpha-internexin promoter, described here, provides a useful animal model to specifically manipulate genes in the developing nervous system [12].

References