Compartmentation of Fyn kinase with glycosylphosphatidylinositol-anchored molecules in oligodendrocytes facilitates kinase activation during myelination.
In many cell types, glycosylphosphatidylinositol (GPI)-anchored proteins are sequestered in detergent-resistant membrane rafts. These are plasma membrane microdomains enriched in glycosphingolipids and cholesterol and are suggested to be platforms for cell signaling. Concomitant with the synthesis of myelin glycosphingolipids, maturing oligodendrocytes progressively associate GPI-anchored proteins, including the adhesion molecules NCAM 120 and F3, in rafts. Here we show that these microdomains include Fyn and Lyn kinases. Both kinases are maximally active in myelin prepared from young animals, correlating with early stages of myelination. In the rafts, Fyn kinase is tightly associated with NCAM 120 and F3. In contrast, in oligodendrocyte progenitor cells lacking rafts or in raft-free membrane domains of more mature cells, F3 does not associate with Fyn. The addition of anti-F3 antibodies to oligodendrocytes results in stimulation of Fyn kinase specifically in rafts. Compartmentation of oligodendrocyte GPI-anchored proteins in rafts is thus a prerequisite for association with Fyn, permitting kinase activation. Interaction of oligodendrocyte F3 with axonal ligands such as L1 and ensuing kinase activation may play a crucial role in initiating myelination.
Krämer
E M
EM
Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Klein
C
C
Koch
T
T
Boytinck
M
M
Trotter
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D058966:Contactins; D003432:Cross-Linking Reagents; D006028:Glycosphingolipids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D003432:Cross-Linking Reagents; D006028:Glycosphingolipids; D017261:Glycosylphosphatidylinositols; D019006:Neural Cell Adhesion Molecules; D011518:Proto-Oncogene Proteins; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases