Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins.
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.
Curtis
R
R
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Adryan
K M
KM
Stark
J L
JL
Park
J S
JS
Compton
D L
DL
Weskamp
G
G
Huber
L J
LJ
Chao
M V
MV
Jaenisch
R
R
Lee
K F
KF
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
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