GALACTOCEREBROSIDE AND SULFATIDE INDEPENDENTLY MEDIATE CA2+ RESPONSES IN OLIGODENDROCYTES

Galactocerebroside (Ga]C) and sulfated galactocerebroside (sulfatide) are sphingolipids highly enriched in myelin. The binding of antibodies reactive with either sulfatide or GalC to cultured oligodendrocytes causes a Ca2+ influx, followed by microtubule depolymerization; however, antisulfatide is less effective than anti-Ga]C in altering cytoskeleton. Typical Ca2+ responses are delayed for both antibodies but are transient for sulfatide-reactive antibodies in contrast to the sustained responses previously reported for anti-Ga]C (Dyer and Benjamins, J Cell Biol 111: 625-633, 1990). Approximately one-half as many oligodendrocytes respond to sulfatide-reactive antibodies (about 39%) as to anti-GalC (about 75%). Subpopulations of oligodendrocytes were identified that responded to neither antibody, only one antibody, or both antibodies, indicating that sulfatide and GalC independently mediate Ca2+ responses. These results suggest that sulfatide and GalC have different physiologic roles in regulating elaboration of myelin membrane by oligodendrocytes in vivo and support the possibility that viral or immune attack via GalC or sulfatide on oligodendrocytes may mimic normal signals in a manner that disrupts the sequence of events that coordinates myelination or maintenance of myelin in vivo.