A new turning point in glycosphingolipid research

Research on glycosphingolipids has advanced with the finding of their involvement in sphingolipidoses, blood group- and differentiation-related antigens, and receptors for bacteria and viruses. Recently, the molecular cloning of genes for the synthesis of glycosphingolipids has been performed extensively, and mice without sugar transferase-genes have been generated. These transferase-null mice have shown that the complex carbohydrate structures of glycosphingolipids are not essential for the embryogenesis, morphogenesis or development of animals, but that the accumulation of an intermediate, such as GM3 or ceramide, causes significant failure of neural development in knockout mice as to the GM2, GD3 and GlcCer synthase genes. On the other hand, the nonreducing terminal carbohydrates in either glycosphingolipids or glycoproteins have been confirmed to be related to carbohydrate-mediated phenomena using the same gene-manipulation technique, indicating that glycosphingolipids are some of the carriers for functionally important carbohydrates. Glycosphingolipids are certainly small molecules with hydrophobic ceramides, which carry both donor and acceptor groups of the hydrogen-bonding region with the potential ability to interact with several proteins on the raft structure in biomembranes, and their dynamic movement in the membranes was revealed by the flip-flop regulation of their synthesis in the Golgi apparatus and the transformation-associated alteration in the reactivity of the carbohydrate moiety with several ligands. Thus, research on the functional significance of glycosphingolipids should be carried out again regarding their physicochemical properties.