Modulation of the neuronal binding of the beta subunit of nerve growth factor (NGF) by the alpha-NGF subunit.
The effect of the alpha subunit of the 7S-NGF on the binding of beta-NGF to its two classes of sites on target cells has been studied. The presence of microM concentrations of alpha-NGF causes the displacement of 125I-beta-NGF from one class of sites on dissociated dorsal root ganglia neurons from stage E9 chicken embryos. At 0.1 nM 125I-beta-NGF, increasing alpha-NGF concentrations produce a monotonic displacement curve with half-maximal displacement occurring at 10 microM alpha-NGF. The affinity and number of sites of the 125I-beta-NGF displaced by alpha-NGF are similar to those of beta-NGF that binds to the higher affinity (site I) receptors. The binding to the lower affinity class of sites (site II) is not affected by concentrations of alpha-NGF up to 30 microM. This modulation of 125I-beta-NGF binding does not occur with equivalent concentrations of serum albumin. No detectable neuronal binding of 125I-alpha-NGF was found, suggesting that the mechanism does not involve direct competition for receptor sites. The dissociation constant for the alpha-beta complex is in the microM range, and formation of this complex in solution can thus compete with the process of 125I-beta-NGF binding to neurons. A model accounting for these observations includes binding of the alpha-beta complex to the lower affinity but not to the higher affinity sites. We conclude that there are differences in the specificity of the two classes of receptors.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002642:Chick Embryo; D005727:Ganglia, Spinal / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor