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 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.
Wang
C
C
Department of Morphology, University of Geneva Medical School, Switzerland.
Pralong
W F
WF
Schulz
M F
MF
Rougon
G
G
Aubry
J M
JM
Pagliusi
S
S
Robert
A
A
Kiss
J Z
JZ
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
D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D012794:Sialic Acids; C021319:polysialic acid; D012313:RNA; D002118:Calcium