title: Glycolipids and transmembrane signaling: antibodies to galactocerebroside cause an influx of calcium in oligodendrocytes.
abstract: This is the first study to provide evidence that one function for the surface glycolipid galactocerebroside (GalC) is participation in the opening of Ca2+ channels in oligodendroglia in culture. This glycolipid is a unique differentiation marker for myelin-producing cells; antibodies to GalC have been shown to markedly alter oligodendroglial morphology via disruption of microtubules (Dyer, C. A., and J. A. Benjamins. 1988. J. Neurosci. 8:4307-4318). This study demonstrates that extracellular EGTA blocks anti-GalC-induced disassembly of microtubules in oligodendroglial membrane sheets, demonstrating that an influx of extracellular Ca2+ mediates the cytoskeletal changes. The Ca2+ influx was examined directly by loading oligodendroglia with the fluorescent dye Indo-1 in defined medium, and measuring changes in Ca2+ in individual cells with a laser cytometer. Upon addition of anti-GalC IgG, a marked sustained increase in intracellular Ca2+ occurred in 80% of the oligodendroglia observed. EGTA blocked the increase, indicating the increase is due to an influx of extracellular Ca2+, and not due to release from intracellular stores. The effect is specific, since Ca2+ levels remain normal in oligodendroglia treated with nonimmune IgG; astrocytes do not respond to the anti-GalC. The Ca2+ response in oligodendrocytes is dependent on concentration of antibody and GalC on the oligodendroglial membrane surface. The Ca2+ influx is not mediated by voltage-sensitive Ca2+ channels: it is not blocked by cadmium, and depolarization with K+ does not mimic the response. The kinetics of the response suggest that second messenger-mediated opening of Ca2+ channels is involved.
authors.affiliation: Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors.forename: C A
authors.initials: CA
authors.lastname: Dyer
authors.forename: J A
authors.initials: JA
authors.lastname: Benjamins
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D001921:Brain / Q000502:physiology / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D002554:Cerebrosides / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D005699:Galactosylceramides / Q000276:immunology / Q000502:physiology*; D008297:Male; D008563:Membrane Lipids / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D015220:Calcium Channels; D002554:Cerebrosides; D005699:Galactosylceramides; D008563:Membrane Lipids; D004533:Egtazic Acid; D002118:Calcium