Neurofilament transport in vivo minimally requires hetero-oligomer formation

J Neurosci. 2003 Oct 15;23(28):9452-8. doi: 10.1523/JNEUROSCI.23-28-09452.2003.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axonal Transport / physiology
  • Axons / metabolism
  • Axons / ultrastructure
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Female
  • Intermediate Filament Proteins
  • Intermediate Filaments / metabolism
  • Intermediate Filaments / ultrastructure
  • Macromolecular Substances
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurofilament Proteins / deficiency
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism*
  • Protein Subunits / metabolism
  • Protein Transport / physiology


  • Carrier Proteins
  • Intermediate Filament Proteins
  • Macromolecular Substances
  • Neurofilament Proteins
  • Protein Subunits
  • alpha-internexin
  • neurofilament protein L
  • neurofilament protein H
  • neurofilament protein M