The fate and function of glycosphingolipid glucosylceramide.
In higher eukaryotes, glucosylceramide is the simplest member and precursor of a fascinating class of membrane lipids, the glycosphingolipids. These lipids display an astounding variation in their carbohydrate head groups, suggesting that glycosphingolipids serve specialized functions in recognition processes. It is now realized that they are organized in signalling domains on the cell surface. They are of vital importance as, in their absence, embryonal development is inhibited at an early stage. Remarkably, individual cells can live without glycolipids, perhaps because their survival does not depend on glycosphingolipid-mediated signalling mechanisms. Still, these cells suffer from defects in intracellular membrane transport. Various membrane proteins do not reach their intracellular destination, and, indeed, some intracellular organelles do not properly differentiate to their mature stage. The fact that glycosphingolipids are required for cellular differentiation suggests that there are human diseases resulting from defects in glycosphingolipid synthesis. In addition, the same cellular differentiation processes may be affected by defects in the degradation of glycosphingolipids. At the cellular level, the pathology of glycosphingolipid storage diseases is not completely understood. Cell biological studies on the intracellular fate and function of glycosphingolipids may open new ways to understand and defeat not only lipid storage diseases, but perhaps other diseases that have not been connected to glycosphingolipids so far.
van Meer
Gerrit
G
Department of Membrane Enzymology, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. g.vanmeer@chem.uu.nl
Wolthoorn
Jasja
J
Degroote
Sophie
S
D000818:Animals; D005963:Glucosylceramides / Q000502:physiology*; D006028:Glycosphingolipids / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000502:physiology*
D005963:Glucosylceramides; D006028:Glycosphingolipids