TrkA mediates an NGF survival response in NGF-independent sensory neurons but not in parasympathetic neurons.
We have investigated the role of trkA, the tyrosine kinase NGF receptor in mediating the survival response of embryonic chicken neurons to NGF. Embryonic trigeminal mesencephalic (TMN) neurons, which normally survive in the presence of BDNF but not NGF, become NGF-responsive when microinjected with an expression vector containing rat trkA cDNA. In contrast, microinjection of CNTF-dependent embryonic ciliary neurons with the same construct does not result in the acquisition of NGF-responsiveness. RT-PCR shows that injected TMN and ciliary neurons do not differ in their ability to express rat trkA mRNA or protein. The failure of injected ciliary neurons to show an NGF-promoted survival response is not due to absence of the low-affinity NGF receptor, p75, in these neurons. Quantitative PCR and immunocytochemistry shows that TMN and ciliary neurons both express p75 mRNA and protein. These findings not only provide the first direct experimental demonstration of trkA mediating a physiological response in an appropriate cell type, i.e. NGF-promoted survival of embryonic neurons, but indicate that not all neurons are able to respond to a trkA-mediated signal transduction event.
Department of Anatomy, St. George's Medical School, London, UK.
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TE
Allsopp
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M
Robinson
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S
Wyatt
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AM
Davies
D000818:Animals; D001483:Base Sequence; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D017931:DNA Primers; D018076:DNA, Complementary; D008562:Membrane Glycoproteins / Q000235:genetics; D008636:Mesencephalon / Q000378:metabolism; D008845:Microinjections; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA