ROLE OF AXONS IN MEMBRANE PHOSPHOLIPID-SYNTHESIS IN RAT SYMPATHETIC NEURONS

The axonal synthesis of phospholipids has been demonstrated in compart mented cultures of rat sympathetic neurons. In this model of neuron cu lture, metabolic events occurring in distal axons were studied indepen dently of those occurring in cell bodies. Using radiolabeled tracers t he axonal biosynthesis of the major membrane phospholipids and fatty a cids but not cholesterol was detected. The capacity of axons for synth esis of phosphatidylcholine (PC), the major membrane lipid, was confir med by the demonstration that key enzymes of PC biosynthesis were pres ent in distal axons. A double-labeling experiment showed that at least 50% of axonal PC was synthesized locally in axons, with the remainder being made in cell bodies and transported into axons. The requirement of axonal PC synthesis for axonal elongation was investigated. When P C biosynthesis in distal axons alone was inhibited by two independent approaches (deprivation of choline or addition of the inhibitor hexade cylphosphocholine) axonal growth was markedly retarded. Our experiment s demonstrated that PC synthesis in cell bodies was neither necessary nor sufficient for growth of distal axons, whereas local synthesis of PC in distal axons was required for normal axonal elongation.