Myelin protein composition is altered in mice lacking either sulfated or both sulfated and non-sulfated galactolipids

Myelin is highly enriched in galactocerebroside (GalCer) and its sulfated form sulfatide. Mice, unable to synthesize GalCer and sulfatide (CGT(null)) or sulfatide alone (CST(null)), exhibit disorganized paranodal structures and progressive dysmyelination. To obtain insights into the molecular mechanisms underlying these defects, we examined myelin composition of these mutants by two-dimensional differential fluorescence intensity gel electrophoresis proteomic approach and immunoblotting. We identified several proteins whose expressions were significantly altered in these mutants. These proteins are known to regulate cytoskeletal dynamics, energy metabolism, vesicular trafficking or adhesion, suggesting a disruption in these physiological processes in the absence of myelin galactolipids. Further analysis of one of these proteins, nucleotide diphosphate kinase (NDK)/Nm23, showed that it was reduced in myelin of CGT(null) and increased in CST(null), but not in whole brain homogenate. Immunostaining showed an increase in its expression in the cell bodies of CGT(null)- and a decrease in CST(null)-oligodenrocytes, together leading to the hypothesis that transport of NDK/Nm23 from oligodenrocyte cell bodies into myelin may be differentially dysregulated in the absence of these galactolipids. This study provides new insights into the changes that occur in the composition/distribution of myelin proteins in mice lacking either unsulfated and/or sulfated galactolipids and reinforces the role of these lipids in intracellular trafficking.