Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration.
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 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.
Kim
Paul M
PM
Department of Pharmacology and Molecular Science, Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Aizawa
Hiroyuki
H
Kim
Peter S
PS
Huang
Alex S
AS
Wickramasinghe
Sasrutha R
SR
Kashani
Amir H
AH
Barrow
Roxanne K
RK
Huganir
Richard L
RL
Ghosh
Anirvan
A
Snyder
Solomon H
SH
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D000099300:Serine Racemase
D002118:Calcium; D002352:Carrier Proteins; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D019998:Racemases and Epimerases; D018091:Receptors, AMPA; D012694:Serine; D000099300:Serine Racemase