title: Dissociation of Axonal Neurofilament Content from Its Transport Rate.
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.
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, United States of America; Department of Psychiatry, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Aidong
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Hassinger
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, United States of America; Department of Psychiatry, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Mala V
authors.initials: MV
authors.lastname: Rao
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université Laval, Département d'anatomie et physiologie de l'Université Laval, Québec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, Kings College London, London, United Kingdom; Clinical Neurosciences, Institute of Psychiatry, Kings College London, London, United Kingdom.
authors.forename: Christopher C J
authors.initials: CC
authors.lastname: Miller
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, United States of America; Department of Psychiatry, New York University School of Medicine, New York, New York, United States of America; Department of Cell Biology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Nixon
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism*; D005260:Female; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009900:Optic Nerve / Q000378:metabolism; D010766:Phosphorylation