Possible roles of glycosphingolipids in lipid rafts.

Recent studies have suggested that glycosphingolipid (GSL)-cholesterol microdomains in cell membranes may function as platforms for the attachment of lipid-modified proteins, such as glycosylphosphatidylinositol (GPI)-anchored proteins and src-family tyrosine kinases. The microdomains are proposed to be involved in membrane trafficking of GPI-anchored proteins and in signal transduction via src-family kinases. Here, the possible roles of GSLs in the physical properties of these microdomains, as well as in membrane trafficking and signal transduction, are discussed. Sphingolipid depletion inhibits the intracellular transport of GPI-anchored proteins in biosynthetic traffic and endocytosis via GPI-anchored proteins. Antibodies against GSLs as well as GPI-anchored proteins co-precipitate src-family kinases. Antibody-mediated cross-linking of GSLs, as well as that of GPI-anchored proteins, induces a transient increase in the tyrosine phosphorylation of several substrates. Thus, GSLs have important roles in lipid rafts.