TY - JOUR
T1 - Serine racemase
T2 - Activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration
AU - Kim, Paul M.
AU - Aizawa, Hiroyuki
AU - Kim, Peter S.
AU - Huang, Alex S.
AU - Wickramasinghe, Sasrutha R.
AU - Kashani, Amir H.
AU - Barrow, Roxanne K.
AU - Huganir, Richard L.
AU - Ghosh, Anirvan
AU - Snyder, Solomon H.
PY - 2005/2/8
Y1 - 2005/2/8
N2 - 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 SR by glutamate neurotransmission involving α-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.
AB - 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 SR by glutamate neurotransmission involving α-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.
KW - D-serine
KW - α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor
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U2 - 10.1073/pnas.0409723102
DO - 10.1073/pnas.0409723102
M3 - Article
C2 - 15684087
AN - SCOPUS:13844306349
SN - 0027-8424
VL - 102
SP - 2105
EP - 2110
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -