Oligodendrocytes direct glycosyl phosphatidylinositol-anchored proteins to the myelin sheath in glycosphingolipid-rich complexes.
The myelin sheath synthesized by oligodendrocytes insulates central nervous system axons and is a specialized subdomain of the plasma membrane, containing a restricted pattern of proteins and lipids. Myelin is enriched in glycosphingolipids and cholesterol, a lipid environment favored by glycosylphosphatidylinositol (GPI)-anchored proteins, which associate with these lipids in detergent-insoluble complexes in many cell types. Since proteins regulating oligodendroglia-neuron interaction are largely unknown and GPI-anchored proteins are often involved in cell-cell interactions, we examined oligodendrocytes and myelin for their expression of these proteins. Oligodendrocyte precursors and maturing oligodendrocytes express a similar pattern of GPI-anchored proteins, which unlike the majority of oligodendrocyte plasma membrane proteins, accumulate in myelin. To elucidate mechanisms underlying the expression of GPI-anchored proteins in myelin, we analyzed detergent-insoluble complexes from cells and myelin using TX-100 extraction and sucrose density gradients. In precursor cells, the GPI-anchored proteins are not incorporated in detergent-insoluble complexes. In contrast, GPI-anchored proteins from maturing oligodendrocytes and from myelin were isolated as complexes associated with glycosphingolipids and cholesterol. These results show a specific association of GPI-anchored proteins with glycosphingolipids and cholesterol during oligodendrocyte maturation and suggest sorting of these macromolecular complexes to myelin.
Krämer
E M
EM
Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Koch
T
T
Niehaus
A
A
Trotter
J
J
D000818:Animals; D001710:Biotin; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006028:Glycosphingolipids / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D017830:Octoxynol; D009836:Oligodendroglia / Q000378:metabolism*
D006028:Glycosphingolipids; D017261:Glycosylphosphatidylinositols; D001710:Biotin; D017830:Octoxynol