Viral transduction of trkA into cultured nodose and spinal motor neurons conveys NGF responsiveness.
The trkA gene encodes the tyrosine kinase receptor that transduces the NGF signal. We have used a defective herpes simplex virus-1 (HSV-1) vector containing a full-length rat trkA sequence (pHSVtrkA) to express NGF receptors in primary cultures of neonatal nodose neurons and embryonic spinal motor neurons which are normally unresponsive to NGF. Transduction of rat neonatal nodose ganglion neurons and spinal motor neurons with pHSVtrkA resulted in expression of functional NGF receptors. Stimulation of these receptors by NGF resulted in the survival and the morphologic and biochemical differentiation of these neurons. These observations indicate that nodose and spinal motor neurons can express the downstream signal transduction apparatus necessary to mediate the survival and differentiating effects mediated by ligand binding to trkA and that transduction with pHSVtrkA can effectively convert NGF nonresponsive neurons into responsive ones.
Xu
H
H
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
Federoff
H
H
Maragos
J
J
Parada
L F
LF
Kessler
J A
JA
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018259:Herpesvirus 1, Human / Q000235:genetics*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009620:Nodose Ganglion / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D014161:Transduction, Genetic
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA