c-Fos activates glycolipid síntesis by activating the first glycosyltransferase of their synthesis

CRESPO PILAR MARÍA; SILVESTRE DAVID C.; MACCIONI HUGO JF; DANIOTTI JOSÉ L; CAPUTTO BEATRIZ L

Mar del Plata, Buenos Aires

Congreso; XLIII Reunión Nacional de la Sociedad Argentina de Investigación en Bioquímica y Biología Celular (SAIB); 2007

It has been demonstrated that c-Fos, 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 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 labelling 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 trasnferase 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.