Biochemical pharmacology of isolated neuronal growth cones: implications for synaptogenesis

The neuronal growth cone is critical to the establishment of neuronal polarity through its motile, pathfinding and target recognition properties exhibited during synaptogenesis. Subcellular fractionation procedures yielding milligram quantities of isolated growth cones has allowed for biochemical and pharmacological investigation of intrinsic growth cone components that are likely to be involved in regulation of growth cone function in neuronal development. These 'mapping' studies of growth cone components are prerequisites to elucidating the mechanisms by which extracellular factors influence the motility, adhesion and directed growth of the growth cone. For example, neurotransmitters and polypeptide growth factors which have been shown in other systems to modulate growth cone behavior are presumed to act through receptors on the growth cone, inducing second-messenger molecule formation and consequent modification and regulation of proteins effecting the response(s) of the growth cone (i.e. proteins involved in motility, adhesion and membrane turnover). In a relatively short period of time, work with the isolated growth cone preparation has identified, in independent studies, many of the elements involved in this proposed scheme of events, including transmitter receptors, second-messenger cascades, and second-messenger post-translational modifications. An obvious future goal will be to analyze in more detail the intracellular events, and the relationships between them, in the growth cone and how they transmit extracellular signals into responses such as motility and adhesivity which underly the growth cone's synaptogenic properties. It is to be expected that much of this information will come forth from experimentation with the isolated growth cone preparation.