Understanding the role of Glucosylceramide in cell signalling

Glucosylceramide (GlcCer) is the simplest member and common precursor of glycosphingolipids (GSLs). It is synthesized by GlcCer synthase (GCS), which catalyzes the glycosylation of ceramide on the cytosolic side of the cis-Golgi membranes. After synthesis GlcCer is translocated to the Golgi lumen for lactosylceramide (LacCer) synthesis and production of more complex GSLs. Spending part of its life on the cytosolic membrane side, GlcCer is available for interaction with cytosolic proteins. In recent years, indeed, proteins intercepting GlcCer during its cytosolic life and influencing its trafficking have been identified. Here we want to understand if GlcCer, like other cytosolically oriented lipids influences intracellular signalling events by intercepting/recruiting cytosolic factors at the Golgi complex. To this aim we have silenced GCS and lactosylceramide synthase (LCS), the enzymes responsible for the production of glucosylceramide and lactosylceramide respectively and evaluated the cellular response to growth factors stimulation. Preliminary experimental evidence shows that GlcCer negatively regulates AKT suggesting a possible involvement of this lipid in growth signalling pathways.