title: Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins.
abstract: The receptor mechanisms mediating the retrograde axonal transport of the neurotrophins have been investigated in adult rats. We show that transport of the TrkB ligands NT-4 and BDNF to peripheral neurons is dependent on the low affinity neurotrophin receptor (LNR). Pharmacological manipulation of LNR in vivo using either an anti-LNR antibody or a soluble recombinant LNR extracellular domain completely blocked retrograde transport of NT-4 and BDNF to sensory neurons, while having minimal effects on the transport of NGF in either sensory or sympathetic neurons. Furthermore, in mice with a null mutation of LNR, the transport of NT-4 and BDNF, but not NGF, was dramatically reduced. These observations demonstrate a selective role for LNR in retrograde transport of the various neurotrophins from distinct target regions in vivo.
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
authors.forename: R
authors.initials: R
authors.lastname: Curtis
authors.forename: K M
authors.initials: KM
authors.lastname: Adryan
authors.forename: J L
authors.initials: JL
authors.lastname: Stark
authors.forename: J S
authors.initials: JS
authors.lastname: Park
authors.forename: D L
authors.initials: DL
authors.lastname: Compton
authors.forename: G
authors.initials: G
authors.lastname: Weskamp
authors.forename: L J
authors.initials: LJ
authors.lastname: Huber
authors.forename: M V
authors.initials: MV
authors.lastname: Chao
authors.forename: R
authors.initials: R
authors.lastname: Jaenisch
authors.forename: K F
authors.initials: KF
authors.lastname: Lee
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001665:Binding Sites; D001692:Biological Transport; D019208:Brain-Derived Neurotrophic Factor; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000502:physiology*; D014909:Wheat Germ Agglutinins / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D018013:Receptors, Neuropeptide; D014909:Wheat Germ Agglutinins; D020794:Receptor Protein-Tyrosine Kinases; C073922:neurotrophin 4