Serine racemase: Activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration

Paul M. Kim, Hiroyuki Aizawa, Peter S. Kim, Alex S. Huang, Sasrutha R. Wickramasinghe, Amir H. Kashani, Roxanne K. Barrow, Richard L. Huganir, Anirvan Ghosh, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2105-2110
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number6
DOIs
StatePublished - Feb 8 2005

Keywords

  • D-serine
  • α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Serine racemase: Activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration'. Together they form a unique fingerprint.

Cite this