Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an αvIntegrin/Myelin Proteolipid Protein Complex

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Abstract
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 αvintegrin-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 αvintegrin modulated the AMPA-stimulated migration, and stimulation of OPC AMPA receptors resulted in increased association of the AMPA receptor subunits themselves with the αvintegrin/PLP complex. Thus, after AMPA receptor stimulation, an αvintegrin/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/αvintegrin 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.