THE ROLES OF CERAMIDE IN THE REGULATION OF NEURONAL GROWTH AND DEVELOPMENT

Ceramide can be formed by the activity of two general metabolic pathwa ys, the anabolic pathway, in which ceramide is formed by acylation of a sphingoid long chain base, and the catabolic pathway, in which ceram ide is formed by the degradation of either glycosphingolipids or of sp hingomyelin (SM). The anabolic reactions take place in the early compa rtments of the secretory pathway (the endoplasmic reticulum and the Go lgi apparatus) and the catabolic reactions rake place either in lysoso mes or at the plasma membrane. Work from our and other laboratories ha s shown that neuronal growth and development can be regulated by manip ulating ceramide metabolism. Thus, synthesis of glucosylceramide from ceramide is required for axonal growth in cultured hippocampal neurons , but the formation of ceramide from SM, by a sphingomyelinase activit y, stimulates the earliest stages of development in these cells, namel y the formation of minor neuronal processes and the initial formation of the axon. Thus, ceramide and its metabolites play distinct roles in the same neuron, depending on the intracellular site of generation of ceramide and on the stage of neuronal development.