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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / enzymology*
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Cerebral Cortex / cytology
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Female
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Glucose / metabolism
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Green Fluorescent Proteins / genetics
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Male
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Mice
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Mice, Transgenic
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Neurons / cytology
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Neurons / enzymology*
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Phosphoglycerate Dehydrogenase / genetics*
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Phosphoglycerate Dehydrogenase / metabolism*
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Primary Cell Culture
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Promoter Regions, Genetic / physiology
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Racemases and Epimerases / genetics
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Racemases and Epimerases / metabolism
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Serine / biosynthesis
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Serine / metabolism*
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Synaptic Transmission / physiology
Substances
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Green Fluorescent Proteins
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Serine
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Phosphoglycerate Dehydrogenase
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Racemases and Epimerases
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serine racemase
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Glucose