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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Aug 15;90(16):7859–7863. doi: 10.1073/pnas.90.16.7859

Differential expression of nerve growth factor receptors leads to altered binding affinity and neurotrophin responsiveness.

M Benedetti 1, A Levi 1, M V Chao 1
PMCID: PMC47242  PMID: 8356095

Abstract

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.

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