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.
MeSH terms
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Animals
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Axonal Transport / physiology*
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Binding Sites
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Biological Transport
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Brain-Derived Neurotrophic Factor
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Ganglia, Spinal / metabolism
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Humans
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Male
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Mice
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Mice, Inbred BALB C
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Motor Neurons / metabolism
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Mutation
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Nerve Growth Factors / metabolism*
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Nerve Tissue Proteins / metabolism*
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Neurons, Afferent / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Ciliary Neurotrophic Factor
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor / metabolism
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Receptors, Neuropeptide / genetics
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Receptors, Neuropeptide / physiology*
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Wheat Germ Agglutinins / metabolism
Substances
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Brain-Derived Neurotrophic Factor
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Nerve Growth Factors
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Nerve Tissue Proteins
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Receptor, Ciliary Neurotrophic Factor
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor
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Receptors, Neuropeptide
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Wheat Germ Agglutinins
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Receptor Protein-Tyrosine Kinases
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neurotrophin 4