Enzymes
| UniProtKB help_outline | 3 proteins |
Reaction participants Show >> << Hide
- Name help_outline D-isoleucine Identifier CHEBI:193151 Charge 0 Formula C6H13NO2 InChIKeyhelp_outline AGPKZVBTJJNPAG-RFZPGFLSSA-N SMILEShelp_outline [O-]C([C@@H]([C@@H](CC)C)[NH3+])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline D-serine Identifier CHEBI:35247 Charge 0 Formula C3H7NO3 InChIKeyhelp_outline MTCFGRXMJLQNBG-UWTATZPHSA-N SMILEShelp_outline [NH3+][C@H](CO)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 18 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:74299 | RHEA:74300 | RHEA:74301 | RHEA:74302 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Neuronal D-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity.
Rosenberg D., Artoul S., Segal A.C., Kolodney G., Radzishevsky I., Dikopoltsev E., Foltyn V.N., Inoue R., Mori H., Billard J.M., Wolosker H.
D-Serine and glycine are coagonists of NMDA receptors (NMDARs), but their relative contributions for several NMDAR-dependent processes are unclear. We now report that the alanine-serine-cysteine transporter-1 (Asc-1) mediates release of both D-serine and glycine from neurons, and, in turn, this mo ... >> More
D-Serine and glycine are coagonists of NMDA receptors (NMDARs), but their relative contributions for several NMDAR-dependent processes are unclear. We now report that the alanine-serine-cysteine transporter-1 (Asc-1) mediates release of both D-serine and glycine from neurons, and, in turn, this modulates NMDAR synaptic activity. Asc-1 antiporter activity is enhanced by D-isoleucine (D-Ile), which releases D-serine and glycine from Asc-1-transfected cells, primary neuronal cultures, and hippocampal slices. D-Ile has no effect on astrocytes, which do not express Asc-1. We show that D-Ile enhances the long-term potentiation (LTP) in rat and mouse hippocampal CA1 by stimulating Asc-1-mediated endogenous D-serine release. D-Ile effects on synaptic plasticity are abolished by enzymatically depleting D-serine or by using serine racemase knock-out (SR-KO) mice, confirming its specificity and supporting the notion that LTP depends mostly on D-serine release. Conversely, our data also disclose a role of glycine in activating synaptic NMDARs. Although acute enzymatic depletion of D-serine also drastically decreases the isolated NMDAR synaptic potentials, these responses are still enhanced by D-Ile. Furthermore, NMDAR synaptic potentials are preserved in SR-KO mice and are also enhanced by D-Ile, indicating that glycine overlaps with D-serine binding at synaptic NMDARs. Altogether, our results disclose a novel role of Asc-1 in regulating NMDAR-dependent synaptic activity by mediating concurrent non-vesicular release of D-serine and glycine. Our data also highlight an important role of neuron-derived D-serine and glycine, indicating that astrocytic D-serine is not solely responsible for activating synaptic NMDARs. << Less
J. Neurosci. 33:3533-3544(2013) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.