Glycosphingolipid structure and function in membranes

Glycosphingolipids (GSLs) are amphiphilic membrane components of all eukaryotic cells. They are located primarily in the plasma membrane and to a lesser extend in intracellular membranes of related organelles. Even some bacteria are known to synthesize GSLs or at least use GSLs generated by hosts. Gangliosides, a group of complex sialic acid-containing GSLs are particularly abundant in the central nervous system. Although gangliosides were long believed to be essential for neuronal function, a groundbreaking step towards understanding their physiological role was the generation of mice models deficient in distinct biosynthetic steps of these complex lipids. During the last 15 - 20 years also the role of their more simple metabolic intermediates like glucosylceramide, ceramide and sphingosine-1-phosphate came into the focus of interest. The present review provides a brief survey of GSL metabolism and intracellular transport, as well as some recent developments regarding ganglioside function in membranes. From the huge amount of data concerning the involvement of gangliosides in various cellular processes, we focused on their role in neurodegeneration and cancer on the one hand and on their function as receptors for toxins or bacteria including the respective elicited signalling pathways on the other hand.