title: D-serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase.
abstract: d-Serine is an endogenous ligand for NMDARs generated from l-serine by the enzyme serine racemase (Srr). Both neuronal and glial localizations have been reported for d-serine and Srr. 3-Phosphoglycerate dehydrogenase is an exclusively astrocytic enzyme that catalyzes the first committed step of l-serine biosynthesis. Using transgenic mice expressing enhanced green fluorescent protein under the Srr promoter and mice with targeted deletion of Srr or 3-Phosphoglycerate dehydrogenase, we demonstrate predominantly neuronal sources of d-serine dependent on astrocytic supply of l-serine. These findings clarify the cellular basis for the regulation of NMDAR neurotransmission by d-serine.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Ehmsen
authors.forename: Ting Martin
authors.initials: TM
authors.lastname: Ma
authors.forename: Hagit
authors.initials: H
authors.lastname: Sason
authors.forename: Dina
authors.initials: D
authors.lastname: Rosenberg
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ogo
authors.forename: Shigeki
authors.initials: S
authors.lastname: Furuya
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.forename: Herman
authors.initials: H
authors.lastname: Wolosker
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D005947:Glucose / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic / Q000502:physiology; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000096:biosynthesis / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D000099300:Serine Racemase
chemical_list: D005947:Glucose; D049452:Green Fluorescent Proteins; D050543:Phosphoglycerate Dehydrogenase; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase