title: 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.
abstract: The capacity for long-distance migration of the oligodendrocyte precursor cell, oligodendrocyte-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-methyl-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.
authors.affiliation: Department of Morphology, University of Geneva Medical School, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: W F
authors.initials: WF
authors.lastname: Pralong
authors.forename: M F
authors.initials: MF
authors.lastname: Schulz
authors.forename: G
authors.initials: G
authors.lastname: Rougon
authors.forename: J M
authors.initials: JM
authors.lastname: Aubry
authors.forename: S
authors.initials: S
authors.lastname: Pagliusi
authors.forename: A
authors.initials: A
authors.lastname: Robert
authors.forename: J Z
authors.initials: JZ
authors.lastname: Kiss
mesh_terms: D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010904:Pituitary Gland, Posterior / Q000166:cytology; D012313:RNA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology
chemical_list: D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D012794:Sialic Acids; C021319:polysialic acid; D012313:RNA; D002118:Calcium