Regulation of Expression of the Low-Affinity NGF Receptor (p75LNGFR) Gene in Clonal Rat Pheochromocytoma PC12h-R Cells and Cultured Rat Basal Forebrain Cholinergic Neurons: Its Relation to Expression of the High-Affinity NGF Receptor (trkA) Gene

Abstract

In the peripheral nervous system nerve growth factor (NGF) is essential for the development and survival of sympathetic and sensory neurons (Greene and Shooter, 1980). Recent studies have indicated that NGF also plays an important role in the development and survival of cholinergic neurons in the basal forebrain (Gnahn et al., 1983; Hatanaka et al., 1988). NGF is a target-derived neurotrophic factor, and therefore is secreted by the target tissue near the nerve terminal. The first step of NGF action is the binding to its receptor. It is known that there are two forms of the NGF receptors, the low-and high-affinity receptors, which bind NGF with Kd values of 10−9 M and 10−11 M, respectively (Misko et al., 1988). Experimental evidence strongly suggests that biological responsiveness to NGF is dependent upon interactions with the high-affinity NGF receptor (Misko et al., 1988). cDNA clones for the low-affity NGF receptor (p75LNGFR) were obtained and sequenced (Johnson et al., 1986; Radeke et al., 1987). The amino acid sequence of the p75LNGFR predicts that the cytoplasmic domain lacks a typical structure for cellular signal transduction like that of tyrosine kinase.