Nerve growth factor receptors on chick embryo sympathetic ganglion cells: binding characteristics and development

Abstract

NGF is essential for the development and maintenance of sympathetic and certain sensory neurons. The NGF receptors on the surface of sympathetic ganglion cells from chick embryos were characterized; they consist of high-affinity receptors with a dissociation constant of about 10(-11) M, and low-affinity receptors with a dissociation constant of about 10(-9) M. There are more than 10 times as many low-affinity as high-affinity receptors per cell. The heterogeneity of NGF binding is not due to negatively cooperative interactions among the receptors. The high- and low-affinity components of NGF binding defined at steady state correspond to slowly and rapidly dissociating components of bound NGF seen in kinetic experiments. In addition, a very slowly dissociating component of bound NGF was observed; this component was a small fraction of binding at low concentrations of NGF but increased to 20-60% of bound NGF at the highest NGF concentrations examined. This very slowly dissociating component of bound NGF accounts for several peculiarities in the binding data not accounted for by steady-state binding of NGF to its high- and low-affinity receptors. Developmental studies showed that both high- and low-affinity NGF receptors were present on chick embryo sympathetic ganglion cells from 6.5 to 20 d in ovo. No significant differences in the numbers or affinities of the receptors were seen with cells from ganglia at 9, 11, or 15 d of development. Cultured non-neuronal cells from sympathetic ganglia had only low-affinity NGF receptors.

The Neurotrophin Receptor p75 Binds Neurotrophin-3 on Sympathetic Neurons with High Affinity and Specificity

“…Indeed, as with other neurotrophins, positive cooperativity has been observed on binding of N T3 to p75 N TR (Rodríguez-Tébar et al, 1992), indicating that p75 N TR exists in (at least) two conformations with different ligand affinities. Consistent with this model, in addition to high-affinity binding sites for NGF and N T3, sympathetic neurons also express p75 N TR low-affinity binding sites for all neurotrophins (Godfrey and Shooter, 1986;Rodriguez-Tébar and Barde, 1988) (our unpublished results). Our results with sympathetic neurons could be explained by a modulation of the ratio between high-and lowaffinity forms of p75 N TR , driven by hitherto unknown molecules in nontransformed cells.…”

Characterization of Histidine Residues Essential for Receptor Binding and Activity of Nerve Growth Factor

“…For example, truncation of the NH 2 -terminal 1-9 residues has now been shown to significantly reduce binding to and phosphorylation of TrkA (34). Moreover, these earlier experiments of DEP modification of NGF (38) measured binding to a microsomal membrane protein preparation from superior cervical ganglia that contains both high and low affinity binding sites (53); therefore, the interpretation of the results is less clear than in cell systems that contain only a single receptor type. In the current study we exploited both site-directed mutagenesis and chemical modification to demonstrate that at least three, and perhaps four, histidine residues play an important role in the structure, receptor binding, and activity of NGF.…”

Frequent expression of 75 kDa nerve growth factor receptor and phosphotyrosine in human peripheral nerve tumours: an immunohistochemical study on paraffin-embedded tissues

“…Previous work has established that two types of nerve growth factor receptors, low and high affinity or fast and slow types, can be distinguished on the neurons of the peripheral nervous system [7,27]. The high affinity receptor is composed of two kinds of low affinity receptor, 75 kDa and 140 kDa in molecular weight, respectively [10,22].…”