Ectopic trkA expression mediates a 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 neurons to NGF. Embryonic trigeminal mesencephalic (TMN) neurons, which normally survive in the presence of brain-derived neurotrophic factor (BDNF) but not NGF, become NGF-responsive when microinjected with an expression vector containing trkA cDNA. In contrast, microinjection of ciliary neurotrophic factor (CNTF)-dependent embryonic ciliary neurons with the same construct does not result in the acquisition of NGF responsiveness by these neurons despite de novo expression of trkA mRNA and protein. The failure of trkA to result in an NGF-promoted survival response in ciliary neurons is not due to absence of the low-affinity NGF receptor, p75, in these neurons. Quantitative RT/PCR and immunocytochemistry showed 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, namely NGF-promoted survival of embryonic neurons, but indicate that not all neurons are able to respond to a trkA-mediated signal transduction event.
Allsopp
T E
TE
School of Biological and Medical Sciences, St. Andrews University, Fife, United Kingdom.
Robinson
M
M
Wyatt
S
S
Davies
A M
AM
D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D002642:Chick Embryo; D017931:DNA Primers / Q000737:chemistry; D005726:Ganglia, Parasympathetic / Q000166:cytology*; D015870:Gene Expression; D008845:Microinjections; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*
D017931:DNA Primers; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA