Studies on the Mechanism of Action of Nerve Growth Factor

Abstract

In this study, explanted chick-embryo sensory ganglia were treated with nerve growth factor, and cellular concentrations of neurotubule protein were measured chemically by a colchicine-binding assay. Even after brief time periods, ganglia treated with growth factor were enriched in neurotubule protein, as compared with untreated (control) ganglia. Furthermore, studies with ganglia treated with both vincristine and growth factor demonstrated that neurotubule protein synthesis can occur even though neurite outgrowth is abolished. Several lines of evidence indicate that the growth factor stimulates de novo synthesis of neurotubule subunit protein, and that this effect precedes neurite extension. Like nerve growth factor, dibutyryl cyclic AMP also stimulates neurite outgrowth from embryonic sensory ganglia, yet it does not increase neurotubule protein levels. Available information suggests that the ability of growth factor to elicit rapid neurite outgrowth is closely related to its ability to increase cellular neurotubule levels. Cyclic AMP appears to stimulate neurite outgrowth by a different mechanism.