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

Kim, Paul M; Aizawa, Hiroyuki; Kim, Peter S; Huang, Alex S; Wickramasinghe, Sasrutha R; Kashani, Amir H; Barrow, Roxanne K; Huganir, Richard L et al. · Proc Natl Acad Sci U S A · 2005

basic_science · Level V

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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 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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