Synthesis of sphingomyelin by oligodendrocytes—how and where?

Sphingomyelin (SM) biosynthesis in cultured oligodendrocytes (OC) was evaluated: (i) with [¹⁴C] tracers (choline, ethanolamine, serine) to pinpoint the major metabolic routes; (ii) with fluorescent and truncated, radiolabeled ceramide analogs to determine the relative activities of SM-synthase in intra- and extra-Golgi compartments of OC. In contrast to a general contention in the literature that SM synthase is absent from the brain, our data show that (choline → CDP-choline → phosphatidylcholine (PC) → SM) is the major anabolic route with only a minor contribution to PC via methylation of phosphatidylethanolamine (PE). SM synthase activity was found to be equally divided between intra- and extra-Golgi compartments of OC. Moreover, significant SM-synthase activity was recovered in purified myelin preparations. Our results shed new light on the possible involvement of sphingolipid-derived mediators in myelination.