It has been demonstrated that c-Fos has, in addition to its well recognized AP-1 transcription factor activity, the capacity to
associate to the ER and activate key enzymes involved in the synthesis of phospholipids required for membrane biogenesis
during cell growth and neurite formation (Gil et al, Mol Biol Cell, 2004). As membrane genesis requires the coordinated supply of all
its integral membrane components, the question emerges of whether c-Fos also activates the synthesis of glycolipids, another ubiquitous
membrane component.We show that c-Fos activates the metabolic labeling of gangliosides in differentiating PC12 cells. Specifically,
c-Fos activates the enzyme Glucosylceramide synthase (GlcCer S), the first glycosylated intermediate in the pathway of glycolipid
synthesis. By contrast, the enzymes Galactosyl transferase 1 (GalT1) and Sialyl transferase 1 (SialT1) are essentially unaffected
by c-Fos. The stimulatory effect of c-Fos on GlcCer S is most noticeable in subcellular fractions containing ER membrane
markers. As c-Fos is not a constitutive component of cells, its expression is tightly regulated by specific environmental cues. This strict
regulation assures that lipid metabolisms activation will occur only when required thus pointing to c-Fos as an important regulator of
key membrane metabolisms during neuronal differentiation.