Neurofilament transport in vivo minimally requires hetero-oligomer formation.
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.
Yuan
Aidong
A
Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York 10962, USA. yuan@nki.rfmh.org
Rao
Mala V
MV
Kumar
Asok
A
Julien
Jean-Pierre
JP
Nixon
Ralph A
RA
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D007381:Intermediate Filament Proteins; D007382:Intermediate Filaments / Q000378:metabolism / Q000648:ultrastructure; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016900:Neurofilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
D002352:Carrier Proteins; D007381:Intermediate Filament Proteins; D046911:Macromolecular Substances; D016900:Neurofilament Proteins; D021122:Protein Subunits; C046643:alpha-internexin; C044882:neurofilament protein L; C051774:neurofilament protein H; C061195:neurofilament protein M