Retrograde axonal transport and lesion-induced upregulation of the TrkA high-affinity NGF receptor.
Long-term physiological responses of nerve growth factor (NGF) and other neurotrophins require gene regulation and likely depend on retrograde axonal transport of NGF or a signaling molecule activated by ligand-receptor interaction. The low-affinity neurotrophin receptor p75LANR is retrogradely transported, but this receptor is not sufficient for NGF-dependent cell survival or differentiation. In this study we examined the distribution and transport of the TrkA NGF receptor using two anti-peptide polyclonal antibodies and a monoclonal antibody, all of which are TrkA specific. We find that (1) in the adult rat brain TrkA-like immunoreactivity is similar with all antibodies in striatal and basal forebrain neurons, (2) TrkA is upregulated in neuronal and nonneuronal cells near the sites of injury, and (3) TrkA immunoreactivity builds up within the proximal and distal segments of transected fimbrial axons, which is consistent with its transport in the anterograde and retrograde directions. Thus, TrkA may itself be, or be a component of, the neurotrophic intraaxonal messenger by which NGF regulates gene expression in sensitive neurons.
Loy
R
R
Department of Neurology, University of Rochester School of Medicine and Dentistry, New York 14620.
Lachyankar
M B
MB
Condon
P J
PJ
Poluha
D K
DK
Ross
A H
AH
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001667:Binding, Competitive; D001692:Biological Transport; D001921:Brain / Q000166:cytology / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009474:Neurons / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D013194:Staining and Labeling; D015854:Up-Regulation
D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D018013:Receptors, Neuropeptide; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA