Glutamate stimulates oligodendrocyte progenitor migration mediated via an alphav integrin/myelin proteolipid protein complex.
In the mammalian CNS, oligodendrocyte precursor cells (OPCs) express most neurotransmitter receptors, but their function remains unclear. The current studies suggest a physiological role for glutamate (AMPA and/or kainate) receptors in OPC migration. AMPA stimulated alphav integrin-mediated OPC migration by increasing both the rate of cell movement and the frequency of Ca2+ transients. A protein complex containing the myelin proteolipid protein (PLP) and alphav integrin modulated the AMPA-stimulated migration, and stimulation of OPC AMPA receptors resulted in increased association of the AMPA receptor subunits themselves with the alphav integrin/PLP complex. Thus, after AMPA receptor stimulation, an alphav integrin/PLP/neurotransmitter receptor protein complex forms that reduces binding to the extracellular matrix and enhances OPC migration. To assess the extent to which PLP was involved in the AMPA-stimulated migration, OPCs from the myelin-deficient (MD) rat, which has a PLP gene mutation, were analyzed. OPCs from the MD rat had a normal basal migration rate, but AMPA did not stimulate the migration of these cells, suggesting that the PLP/alphav integrin complex was important for the AMPA-mediated induction. AMPA-induced modulation of OPC migration was abolished by pertussis toxin, although baseline migration was normal. Thus, G-protein-dependent signaling is crucial for AMPA-stimulated migration of OPCs but not for basal OPC migration. Other signaling pathways involved in this AMPA-stimulated OPC migration were also determined. These studies highlight novel signaling determinants of OPC migration and suggest that glutamate could play a pivotal role in regulating integrin-mediated OPC migration.
Gudz
Tatyana I
TI
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Komuro
Hitoshi
H
Macklin
Wendy B
WB
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001569:Benzodiazepines / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D039564:Integrin alphaV / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008954:Models, Biological; D018991:Myelin Proteolipid Protein / Q000502:physiology*; D009186:Myelin Sheath / Q000235:genetics; D009836:Oligodendroglia / Q000187:drug effects*; D037342:Pertussis Toxin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects*; D019284:Thapsigargin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D002614:Chelating Agents; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005353:Fibronectins; D039564:Integrin alphaV; D007476:Ionophores; D018991:Myelin Proteolipid Protein; D011810:Quinoxalines; D018091:Receptors, AMPA; C061950:GYKI 52466; D012430:Ruthenium Red; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D018698:Glutamic Acid; D004533:Egtazic Acid; D019284:Thapsigargin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002217:Carbachol; D037342:Pertussis Toxin; D020796:Receptor, Platelet-Derived Growth Factor alpha; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007608:Kainic Acid; D002118:Calcium