Differential expression of nerve growth factor receptors leads to altered binding affinity and neurotrophin responsiveness.
The low-affinity p75 neurotrophin receptor is believed to participate with the Trk receptor tyrosine kinase in the formation of high-affinity binding sites for nerve growth factor (NGF). To investigate the functional significance of the two NGF receptors, a truncated p75 receptor was stably expressed in PC12 rat pheochromocytoma cells, yielding cells with greatly reduced levels of wild-type p75 and normal Trk levels. Although these cells were capable of normal differentiation by NGF, very few high-affinity NGF binding sites were detected. These findings indicate that high-affinity binding may be functionally dissociated from biological responses. Furthermore, an increased responsiveness to neurotrophin 3 was observed, as manifested by increased neurite outgrowth. These results suggest that a correct ratio of p75 and p140trk is required to create high-affinity sites and that p75 expression may assist in the discrimination between related but different neurotrophin factors.
Benedetti
M
M
Istituto di Neurobiologia, Consiglio Nazionale delle Ricerche, Rome, Italy.
Levi
A
A
Chao
M V
MV
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D007700:Kinetics; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3; D015513:Oncogene Proteins / Q000378:metabolism; D016716:PC12 Cells; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D015513:Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; C065400:oncogene protein trk; D011505:Protein-Tyrosine Kinases