Linked Life Data

17005864

Source:http://linkedlifedata.com/resource/pubmed/id/17005864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2006-9-28
pubmed:abstractText
Alpha-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 alpha-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 alpha-internexin and neurofilament triplet form separate filament systems. Here, we demonstrate, however, that despite a postnatal decline in expression, alpha-internexin is as abundant as the triplet in the adult CNS and exists in a relatively fixed stoichiometry with these subunits. Alpha-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. Alpha-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 alpha-internexin transport and content in axons throughout the CNS. Moreover, deleting alpha-internexin potentiates the effects of NF-M deletion on NF-H and NF-L transport. Finally, overexpressing a NF-H-LacZ fusion protein in mice induces alpha-internexin and neurofilament triplet to aggregate in neuronal perikarya and greatly reduces their transport and content selectively in axons. Our data show that alpha-internexin and the neurofilament proteins are functionally interdependent. 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10006-19
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17005864-Animals, pubmed-meshheading:17005864-Axons, pubmed-meshheading:17005864-Crosses, Genetic, pubmed-meshheading:17005864-Female, pubmed-meshheading:17005864-Intermediate Filament Proteins, pubmed-meshheading:17005864-Intermediate Filaments, pubmed-meshheading:17005864-Male, pubmed-meshheading:17005864-Mice, pubmed-meshheading:17005864-Mice, Inbred C57BL, pubmed-meshheading:17005864-Mice, Knockout, pubmed-meshheading:17005864-Microscopy, Confocal, pubmed-meshheading:17005864-Microscopy, Fluorescence, pubmed-meshheading:17005864-Microscopy, Immunoelectron, pubmed-meshheading:17005864-Multiprotein Complexes, pubmed-meshheading:17005864-Nerve Degeneration, pubmed-meshheading:17005864-Neurofilament Proteins, pubmed-meshheading:17005864-Protein Interaction Mapping, pubmed-meshheading:17005864-Protein Transport, pubmed-meshheading:17005864-Rats, pubmed-meshheading:17005864-Recombinant Fusion Proteins, pubmed-meshheading:17005864-Retinal Ganglion Cells, pubmed-meshheading:17005864-Spinal Cord, pubmed-meshheading:17005864-Structure-Activity Relationship, pubmed-meshheading:17005864-Transfection
pubmed:year
2006
pubmed:articleTitle
Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS.
pubmed:affiliation
Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA. yuan@nki.rfmh.org
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural