The roles of ceramide in the regulation of neuronal growth and development.

Ceramide can be formed by the activity of two general metabolic pathways, the anabolic pathway, in which ceramide is formed by acylation of a sphingoid long chain base, and the catabolic pathway, in which ceramide is formed by the degradation of either glycosphingolipids or of sphingomyelin (SM). The anabolic reactions take place in the early compartments of the secretory pathway (the endoplasmic reticulum and the Golgi apparatus) and the catabolic reactions take place either in lysosomes or at the plasma membrane. Work from our and other laboratories has shown that neuronal growth and development can be regulated by manipulating 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 activity, stimulates the earliest stages of development in these cells, namely 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.