Differential utilization of the ethanolamine moiety of phosphatidylethanolamine derived from serine and ethanolamine during NGF-induced neuritogenesis of PC12 cells

Neurite elongation involves the expansion of the plasma membrane and phosph olipid synthesis. We investigated membrane phosphatidylethanolamine (PE) bi osynthesis in PC12 cells during neurite outgrowth induced by nerve growth f actor (NGF). When PE was prelabeled with [H-3]ethanolamine and the radioact ivity was chased by incubation with 1 mM unlabeled ethanolamine, the radioa ctivity of [H-3]PE steadily declined and [H-3]ethanolamine was released int o the medium in NGF-treated cells during neurite outgrowth; in the absence of unlabeled ethanolamine, the radioactivity of [H-3]PE remained relatively constant for at least 24 hr. In undifferentiated cells but not in NGF-trea ted cells, [H-3]phosphoethanol amine accumulated in significant amounts dur ing pulse labeling, and was converted partly to PE but largely released int o the medium irrespective of incubation with unlabeled ethanolamine. The de cline in the radioactivity of [H-3]PE and release of [H-3]ethanolamine foll owing incubation with unlabeled ethanolamine were also observed in undiffer entiated cells. Thus, the ethanolamine moiety of PE derived from ethanolami ne is actively recycled in both differentiated and undifferentiated cells. When PE was derived from [3H]serine through phosphatidylserine (PS) decarbo xylation, the decrease in radioactivity of [H-3]PE and release of [H-3]etha nolamine into the medium following incubation with unlabeled ethanolamine w ere observed only in NGF-treated cells, but not in undifferentiated cells, indicating that the ethanolamine moiety of PE derived from PS is actively r ecycled only in the cells undergoing NGF-induced neuritogenesis. Thus, in P C12 cells, the ethanolamine moiety of PE derived from PS is regulated diffe rently from that of PE derived from ethanolamine.