The Interaction of Nerve Growth Factor with Its Specific Receptors

Abstract

Although it has long been known that the development of nerve cells is influenced by interactions with target cells and surrounding nonneuronal cells, it is only recently that the problem has been explored at the molecular level. It is becoming increasingly clear that at least some of these interactions are mediated by macromolecular substances, usually proteins, secreted by one or more of the cell types (Varon and Bunge, 1978; Gottlieb and Glaser, 1980). The classic example of such substances is nerve growth factor (NGF). Although originally described for its role in regulating the development of sympathetic and some sensory neurons (Levi-Montalcini and Angeletti, 1968), NGF is equally involved in target cell-neuron communication, which controls the growth of axons and the maintenance and metabolic state of the differentiated neuron (Thoenen and Barde, 1980). Different experimental protocols have been used to define these various roles of NGF. Thus, removal of circulating NGF with anti-NGF antibody completely inhibits the development of sympathetic neurons in newborn rats or mice (Levi-Montalcini and Angeletti, 1968) or partially inhibits sensory-neuron development in the fetus (Gorin and Johnson, 1979). Growing sympathetic axons recover from transection only if sufficient NGF is available at the site of injury (Hendry, 1975). Injection of [¹²⁵I]-NGF into a target organ, e.g., the smooth muscle of the iris, demonstrates the specific uptake of the labeled NGF by sympathetic terminals and its retrograde flow to the neuronal cell body, while biochemical analyses of these cell bodies reveals the regulation of neurotransmitter synthesis by the transported NGF (Thoenen and Barde, 1980).