Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine.

J.-P. Mothet, L. Pollegioni, G. Ouanounou, M. Martineau, P. Fossier, G. Baux
Proceedings of the National Academy of Sciences. 2005-03-30; 102(15): 5606-5611
DOI: 10.1073/pnas.0408483102

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1. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5606-11. Epub 2005 Mar 30.

Glutamate receptor activation triggers a calcium-dependent and SNARE
protein-dependent release of the gliotransmitter D-serine.

Mothet JP(1), Pollegioni L, Ouanounou G, Martineau M, Fossier P, Baux G.

Author information:
(1)Laboratoire de Neurobiologie Cellulaire et Moléculaire, Centre National de la
Recherche Scientifique Unité Propre de Recherche 9040, Institut Fédératif de
Neurobiologie Alfred Fessard, F-91198 Gif-sur-Yvette, France.

The gliotransmitter D-serine is released upon
(S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate and
metabotropic glutamate receptor stimulation, but the mechanisms involved are
unknown. Here, by using a highly sensitive bioassay to continuously monitor
extracellular D-serine levels, we have investigated the pathways used in its
release. We reveal that D-serine release is inhibited by removal of extracellular
calcium and augmented by increasing extracellular calcium or after treatment with
the Ca(2+) ionophore A23187. Furthermore, release of the amino acid is
considerably reduced after depletion of thapsigargin-sensitive intracellular
Ca(2+) stores or chelation of intracellular Ca(2+) with
1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetate-acetoxymethyl ester.
Interestingly, D-serine release also was markedly reduced by concanamycin A, a
vacuolar-type H(+)-ATPase inhibitor, indicating a role for the vesicular proton
gradient in the transmitter storage/release. In addition, agonist-evoked D-serine
release was sensitive to tetanus neurotoxin. Finally, immunocytochemical and
sucrose density gradient analysis revealed that a large fraction of D-serine
colocalized with synaptobrevin/VAMP2, suggesting that it is stored in
VAMP2-bearing vesicles. In summary, our study reveals the cellular mechanisms
subserving D-serine release and highlights the importance of the glial cell
exocytotic pathway in influencing CNS levels of extracellular D-serine.

DOI: 10.1073/pnas.0408483102
PMCID: PMC556243
PMID: 15800046 [Indexed for MEDLINE]

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