Abstract
Glycosphingolipids are membrane components consisting of hydrophobic ceramide and hydrophilic sugar moieties. They cluster with sphingomyelin and cholesterol in cell membrane to form glycosphingolipid-enriched microdomains. Biochemical analyses have demonstrated that glycosphingolipid-enriched microdomains contain several kinds of transducer molecules, especially membrane-anchored signal transduction molecules such as Src family kinases. Although it has been speculated that glycosphingolipids are closely associated with cell differentiation, proliferation and functions such as adhesion, there is quite a lot of evidence that glycosphingolipids by themselves directly mediate signal transductions, which lead to cell functions. Glycosignaling domains (GSDs) have been identified as glycosphingolipid-mediated signal transduction units in mouse melanoma B 16 cells, mouse neuroblastoma Neuro2a cells and human neutrophils. In those cells, certain kinds of glycosphingolipids, e.g. LacCer for neutrophils, are highly expressed on cell surfaces, and associated with Src family kinases in GSD. Glycosphingolipids in GSD specifically recognize carbohydrate epitopes of ligands and mediate cell functions such as adhesion and superoxide generation. Unlike other types of microdomains, GSD-mediated cell functions and associated signaling are not reduced or abolished in the presence of either filpin or methyl-β-cycrodextrip, which are cholesterol-binding reagents known in general to abolish microdomain structures and their functions. The remaining problem to be solved is how glycosphingolipids transmit signal transduction molecules in GSD
