Functional N-Methyl-D-Aspartate Receptors in O-2A Glial Precursor Cells: A Critical Role in Regulating Polysialic Acid-Neural Cell Adhesion Molecule Expression and Cell Migration

• Published in: The Journal of cell biology 1996-12, Vol.135 (6), p.1565-1581
• Main Authors: Wang, Cheng, William-F. Pralong, Schulz, Marie-Françoise, Rougon, Geneviève, Aubry, Jean-Michel, Pagliusi, Sonja, Robert, Antoine, Kiss, Jozsef Z.
• Format: Article
• Language: English
• Subjects: Calcium - metabolism; Cell lines; Cell Movement; Cells; Cells, Cultured; Cellular biology; Cultured cells; Humans; Molecular biology; N methyl D aspartate receptors; Neural cell adhesion molecules; Neural Cell Adhesion Molecules - metabolism; Neuroglia; Neurons; Oligodendroglia; Oligodendroglia - cytology; Oligodendroglia - metabolism; Patch-Clamp Techniques; Pituitary Gland, Posterior - cytology; Receptors; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Recombinant Proteins - metabolism; RNA - metabolism; Sialic Acids - metabolism; Stem cells; Stem Cells - cytology
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.135.6.1565

The capacity for long-distance migration of the oligodendrocyte precursor cell, oligondendrocyte-type 2 astrocyte (O-2A), is essential for myelin formation. To study the molecular mechanisms that control this process, we used an in vitro migration assay that uses neurohypophysial explants. We provide evidence that O-2A cells in these preparations express functional N-mehtyl-D-aspartate (NMDA) receptors, most likely as homomeric complexes of the NR1 subunit. We show that NMDA evokes an increase in cytosolic Ca2+that can be blocked by the NMDA receptor antagonist AP-5 and by Mg2+. Blocking the activity of these receptors dramatically diminished O-2A cell migration from explants. We also show that NMDA receptor activity is necessary for the expression by O-2A cells of the highly sialylated polysialic acid-neural cell adhesion molecule (PSA-NCAM) that is required for their migration. Thus, glutamate or glutamate receptor ligands may regulate O-2A cell migration by modulating expression of PSA-NCAM. These studies demonstrate how interactions between ionotropic receptors, intracellular signaling, and cell adhesion molecule expression influence cell surface properties, which in turn are critical determinants of cell migration.