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α-Internexin Is Structurally and Functionally Associated with the Neurofilament Triplet Proteins in the Mature CNS.
- Source :
- Journal of Neuroscience; 9/27/2006, Vol. 26 Issue 39, p10006-10019, 14p, 7 Diagrams, 4 Graphs
- Publication Year :
- 2006
-
Abstract
- α-Internexin, a neuronal intermediate filament protein implicated in neurodegenerative disease, coexists with the neurofilament (NF) triplet proteins (NF-L, NF-M, and NF-H) but has an unknown function. The earlier peak expression of α-internexin than the triplet during brain development and its ability to form homopolymers, unlike the triplet, which are obligate heteropolymers, have supported a widely held view that α-internexin and neurofilament triplet form separate filament systems. Here, we demonstrate, however, that despite a postnatal decline in expression, α-internexin is as abundant as the triplet in the adult CNS and exists in a relatively fixed stoichiometry with these subunits. α-Internexin exhibits transport and turnover rates identical to those of triplet proteins in optic axons and colocalizes with NF-M on single neurofilaments by immunogold electron microscopy. α-Internexin also coassembles with all three neurofilament proteins into a single network of filaments in quadruple-transfected SW13vim(--) cells. Genetically deleting NF-M alone or together with NF-H in mice dramatically reduces α-internexin transport and content in axons throughout the CNS. Moreover, deleting α-internexin potentiates the effects of NF-M deletion on NF-Hand NF-L transport. Finally, overexpressing a NF-H-LacZ fusion protein in mice induces α-internexin and neurofilament triplet to aggregate in neuronal perikarya and greatly reduces their transport and content selectively in axons. Our data show that α-internexin and the neurofilament proteins are functionally interdependent. The results strongly support the view that α-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 26
- Issue :
- 39
- Database :
- Complementary Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 22750062
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.2580-06.2006