Role of Galactosylceramide and Sulfatide in Oligodendrocytes and CNS Myelin: Formation of a Glycosynapse

Abstract

The two major glycosphingolipids of myelin, galactosylceramide (GalC) and sulfatide (SGC), interact with each other by trans carbohydrate-carbohydrate interactions in vitro. They face each other in the apposed extracellular surfaces of the multilayered myelin sheath produced by oligodendrocytes and could also contact each other between apposed oligodendrocyte processes. Multivalent galactose and sulfated galactose, in the form of GalC/SGC-containing liposomes or silica nanoparticles conjugated to galactose and galactose-3-sulfate, interact with GalC and SGC in the membrane sheets of oligodendrocytes in culture. This interaction causes transmembrane signaling, loss of the cytoskeleton and clustering of membrane domains, similar to the effects of cross-linking by anti-GalC and anti-SGC antibodies. These effects suggest that GalC and SGC could participate in glycosynapses, similar to neural synapses or the immunological synapse, between GSL-enriched membrane domains in apposed oligodendrocyte membranes or extracellular surfaces of mature myelin. Formation of such glycosynapses in vivo would be important for myelination and/or oligodendrocyte/myelin function.