Glycosphingolipids are building blocks for biological membranes and key contributors to their properties. They have roles stretching from cell development and differentiation to cell death. Viral and microbial infections, oncogenesis and lipid storage diseases require glycosphingolipids or are caused by defects in their degradation. The synthesis of their precursor ceramide starts in the endoplasmic reticulum (ER) and the different classes diverge during their glycosylation in the Golgi apparatus.
The structural diversity of glycosphingolipids, combined with their poor water solubility, require special transport systems. The largescale intracellular lipid transport progresses through vesicular routes, whereas targeted transport with high specificity is carried out by lipid transfer proteins.
Our short-term goals are to determine if the glycolipid transfer protein GLTP binding to VAP proteins is regulated by the type of bound lipid. We want to resolve how the GLTP binding to VAP influences the trafficking of cargo inside the cell from the ER to the cell membrane. We will also determine why GLTP is missing in brain cells that lack ceramide synthase 2, the enzyme responsible for making glycosphingolipids in the brain, in particular galactosylceramide the major lipid component of myelin.
Our long-term goal is to determine what other proteins GLTP is interacting with and how this protein-protein interaction is regulated. We are well equipped to answer all these questions and have been working in the field for a long time. The proposed projects are directly based on our previous findings. This research is very important because we are currently the only team that works with the glycolipid transfer proteins and its role in the molecular biology and medicine of sphingolipids.
