Dissociation of Axonal Neurofilament Content from Its Transport Rate.

TitleDissociation of Axonal Neurofilament Content from Its Transport Rate.
Publication TypeJournal Article
Year of Publication2015
AuteursYuan, A, Hassinger, L, Rao, MV, Julien, J-P, Miller, CCJ, Nixon, RA
JournalPLoS One
Volume10
Issue7
Paginatione0133848
Date Published2015
ISSN1932-6203
KeywordsAnimals, Axonal Transport, Axons, Female, Humans, Intermediate Filaments, Male, Mice, Mice, Knockout, Mice, Transgenic, Optic Nerve, Phosphorylation
Abstract

The axonal cytoskeleton of neurofilament (NF) is a long-lived network of fibrous elements believed to be a stationary structure maintained by a small pool of transported cytoskeletal precursors. Accordingly, it may be predicted that NF content in axons can vary independently from the transport rate of NF. In the present report, we confirm this prediction by showing that human NFH transgenic mice and transgenic mice expressing human NFL Ser55 (Asp) develop nearly identical abnormal patterns of NF accumulation and distribution in association with opposite changes in NF slow transport rates. We also show that the rate of NF transport in wild-type mice remains constant along a length of the optic axon where NF content varies 3-fold. Moreover, knockout mice lacking NFH develop even more extreme (6-fold) proximal to distal variation in NF number, which is associated with a normal wild-type rate of NF transport. The independence of regional NF content and NF transport is consistent with previous evidence suggesting that the rate of incorporation of transported NF precursors into a metabolically stable stationary cytoskeletal network is the major determinant of axonal NF content, enabling the generation of the striking local variations in NF number seen along axons.

DOI10.1371/journal.pone.0133848
Alternate JournalPLoS ONE
PubMed ID26208164
PubMed Central IDPMC4514674
Grant ListR01 AG005604 / AG / NIA NIH HHS / United States
AG05604 / AG / NIA NIH HHS / United States
/ / Medical Research Council / United Kingdom
G0501573 / / Medical Research Council / United Kingdom
R37 AG005604 / AG / NIA NIH HHS / United States
/ / Wellcome Trust / United Kingdom