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

摘要

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.