title: The C-terminal domains of NF-H and NF-M subunits maintain axonal neurofilament content by blocking turnover of the stationary neurofilament network.
abstract: Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF) subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M)(tailΔ)] mice that the deletion of both of these domains selectively lowers NF levels 3-6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M)(tailΔ) mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M)(tailΔ) axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, United States of America. rao@nki.rfmh.org
authors.forename: Mala V
authors.initials: MV
authors.lastname: Rao
authors.forename: Aidong
authors.initials: A
authors.lastname: Yuan
authors.forename: Jabbar
authors.initials: J
authors.lastname: Campbell
authors.forename: Asok
authors.initials: A
authors.lastname: Kumar
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Nixon
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D005260:Female; D015151:Immunoblotting; D008297:Male; D051379:Mice; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; C051774:neurofilament protein H; C061195:neurofilament protein M