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

The capacity for long-distance migration of the oligodendrocyte precur sor cell, oligondendrocyte-type 2 astrocyte (O-2A), is essential for m yelin formation. To study the molecular mechanisms that control this p rocess, we used an in vitro migration assay that uses neurohypophysial explants. We provide evidence that O-2A cells in these preparations e xpress functional N-mehtyl-D-aspartate (NMDA) receptors, most likely a s homomeric complexes of the NR1 subunit. We show that NMDA evokes an increase in cytosolic Ca2+ that can be blocked by the NMDA receptor an tagonist AP-5 and by Mg2+. Blocking the activity of these receptors dr amatically diminished O-2A cell migration from explants. We also show that NMDA receptor activity is necessary for the expression by O-2A ce lls of the highly sialylated polysialic acid-neural cell adhesion mole cule (PSA-NCAM) that is required for their migration. Thus, glutamate or glutamate receptor ligands may regulate O-2A cell migration by modu lating expression of PSA-NCAM. These studies demonstrate how interacti ons between ionotropic receptors, intracellular signaling, and cell ad hesion molecule expression influence cell surface properties, which in turn are critical determinants of cell migration.