A composite diagram summarizing features of CNS myelin: i). architecture of CNS myelin; ii) molecular composition of CNS myelin (three-dimensional view) and; iii.) the unique sphingosine 3-O-acetylated-GalCer glycolipid series. The myelin is a multi-layer membrane formed by oligodendrocytes, containing a high lipid (80%) to protein (20%) ratio and an asymmetric distribution of lipids (PLP: Proteolipid protein; MBP: Myelin basic protein; MOG: Myelin oligodendrocyte glycoprotein; MAG: Myelin-associated glycoprotein; CNP: 2’3’-cyclic-nucleotide 3’-phospodiesterase). The diagram depicts a hypothetical arrangement according to molar compositions of complex lipids (cholesterol, phospholipids and glycolipids) and the most abundant proteins (PLP, MBP) in the CNS myelin bilayer. The relative constancy of molar proportions of the three lipid classes: cholesterol (C): phospholipids (PLs): galactocerebrosides (GalCer) distributed in bilayers is C: PLs: GalCer=2:2:1. Proteins abbreviated as above are marked in yellow and the comprising lipids are as follows: cholesterol in orange, phospholipids in pink and the glycosphingolipids (FMC: Fast migrating cerebrosides; GalCer: Galactosylceramide; GM1: Mono-sialoganglioside; GM4: Sialosyl-galactosylceramide; sGalCer: sulfatide) in blue.
Structures of myelin acetyl-cerebrosides (FMCs) are shown at the top. Seven GalCer derivatives, have been characterized in vertebrate brain myelin including human. FMC-1/-2 are 3-O- acetyl-sphingosine derivatives, FMC-3/-4 add 6-O-acetyl-galactose, and the complex FMC-5/-6/-7 are 2,3,4,6-tetra-O-acetyl-GalCers. Penta- and hexa-acetylated complex FMCs are hydrophobic lipids capable of affecting myelin membrane curvature, lipid interactions, and immune reactivity.
Adapted and modified from Podbielska et al. [5].