EVIDENCE THAT THE MAJOR MEMBRANE-LIPIDS, EXCEPT CHOLESTEROL, ARE MADEIN AXONS OF CULTURED RAT SYMPATHETIC NEURONS

Membrane lipids and proteins required for axonal growth and regenerati on are generally believed to be synthesized in the cell bodies of neur ons and transported into the axons. However, we have demonstrated rece ntly that, in cultured rat sympathetic neurons, axons themselves have the capacity to synthesize phosphatidylcholine, sphingomyelin, and pho sphatidylethanolamine. In these experiments, we employed a compartment model of neuron culture in which pure axons grow in a fluid environme nt separate from that containing the cell bodies. In the present study , we again used compartmented cultures to confirm and extend the previ ous results. We have shown that three enzymes of phosphatidylcholine b iosynthesis via the CDP-choline pathway are present in axons. We have also shown that the rate-limiting step in the biosynthesis of phosphat idylcholine by this route in neurons, and locally in axons, is catalyz ed by the enzyme CTP:phosphocholine cytidylyltransferase. The biosynth esis of other membrane lipids, such as phosphatidylserine, phosphatidy lethanolamine derived by decarboxylation of phosphatidylserine, phosph atidylinositol, and fatty acids, also occurs in axons. However, the me thylation pathway for the conversion of phosphatidylethanolamine into phosphatidylcholine appears to be a quantitatively insignificant route for phosphatidylcholine synthesis in neurons. Moreover, our data prov ided no evidence for the biosynthesis of another important membrane li pid, cholesterol, in axons.