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Neurofilament transport in vivo minimally requires hetero-oligomer formation.

Publication Type:

Journal Article

Source:

J Neurosci, Volume 23, Issue 28, p.9452-8 (2003)

Keywords:

Animals, Axonal Transport, Axons, Carrier Proteins, Female, Intermediate Filament Proteins, Intermediate Filaments, Macromolecular Substances, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurofilament Proteins, Protein Subunits, Protein Transport

Abstract:

<p>Neurofilament assembly requires at minimum the polymerization of neurofilament light chain (NF-L) with either neurofilament medium chain (NF-M) or neurofilament heavy chain (NF-H) subunits, but requirements for their axonal transport have long been controversial. Using a gene deletion approach, we generated mice containing only NF-L or NF-M. In vivo pulse radiolabeling analyses in retinal ganglion cell neurons revealed that NF-L alone is incapable of efficient transport, whereas nearly one-half of the normal level of NF-M is transported along optic axons in the absence of the other triplet subunits. Under these conditions, however, NF-M transport is completely abolished by deleting alpha-internexin. Our results strongly suggest that efficient neurofilament protein transport in vivo minimally requires hetero-oligomer formation. They also show that NF-M can partner with intermediate filament proteins other than the NF-H and NF-L subunits in neurons to support slow transport and possibly other functions of neuronal intermediate filaments.</p>

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