Role of very long fatty acid-containing glycosphingolipids in membrane organization and cell signaling: the model of lactosylceramide in neutrophils

Glycosphingolipids are highly enriched in specialized membrane microdomains (lipid rafts, caveolar domains and glycosynapses), and they participate to the process of transduction of information across the membrane. Lactosylceramide (LacCer) is specifically coupled with the Src family kinase Lyn in plasma membrane microdomains of human neutrophils. Ligand binding to LacCer activates Lyn, resulting in neutrophil functions, such as superoxide generation and migration. The beta-Gal-(1-4)-beta-Glc disaccharide structure of LacCer is necessary, but it is not sufficient for LacCer-mediated Lyn activation. For this function, the presence of a LacCer molecular species with ceramide containing a very long fatty acid chain is also required. In this manuscript, we discuss the importance of interdigitation within the membrane, promoted by the presence of glycosphingolipid species with very long fatty acyl chains as determinants for membrane organization, instrumental to the signaling process.