47] Sphingolipid photoaffinity labels

Abstract

Glycosphingolipids (GSLs) are components of eukaryotic plasma membranes anchored in the lipid bilayer by a hydrophobic ceramide moiety and expose a hydrophilic oligosaccharide chain into the extracellular space. Variations in the type, number, and linkage of sugar residues in the oligosaccharide chain give rise to the wide range of naturally occurring GSLs. These form cell-type-specific patterns at the cell surface that change with cell growth, differentiation, viral transformation, and oncogenesis. At the cell surface, GSLs can interact with toxins, viruses, and bacteria, as well as with membrane-bound receptors and enzymes. They are also involved in cell-type-specific adhesion processes. In addition, lipophilic products of GSL metabolism, such as sphingosine-1-phosphate and ceramide, play a role in signal transduction events. GSLs form a protective layer on biological membranes, protecting them from inappropriate degradation. This chapter discusses photoaffinity ligands that have been used for the identification of (glyco)sphingolipid receptors or for the analysis of (glyco)sphingolipid metabolism. This includes the determination of binding sites within sphingolipid-binding proteins. Applications and some basic problems associated with this approach are discussed.