Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 6, Pages 2105-2110Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409723102
Keywords
alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor D-serine
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Funding
- NIDA NIH HHS [DA00074, K05 DA000074] Funding Source: Medline
- NIMH NIH HHS [R37 MH018501, MH18501, R01 MH018501] Funding Source: Medline
- NINDS NIH HHS [NS39993, NS036715, R01 NS036715] Funding Source: Medline
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Serine racemase (SR), localized to astrocytic glia that ensheathe synapses, converts L-serine to D-serine, an endogenous ligand of the NMDA receptor. We report the activation of SIR by glutamate neurotransmission involving alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors via glutamate receptor interacting protein (GRIP) and the physiologic regulation of cerebellar granule cell migration by SR. GRIP physiologically binds SR, augmenting SR activity and D-serine release. GRIP infection of neonatal mouse cerebellum in vivo enhances granule cell migration. Selective degradation Of D-serine by D-amino acid oxidase and pharmacologic inhibition of SR impede migration, whereas D-serine activates the process. Thus, in neuronal migration, glutamate stimulates Bergmann glia to form and release D-serine, which, together with glutamate, activates NMDA receptors on granule neurons, chemokinetically enhancing migration.
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