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.