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

• DOI: 10.1073/pnas.0408483102
• Publication Date: 2005-03-31T01:24:44Z
• Authors: Jean-Pierre Mothet; Loredano Pollegioni; Gilles Ouanounou; Magalie Martineau; Philippe Fossier; Gérard Baux
• Keywords: Kainate receptor

The gliotransmitter d -serine is released upon (S)-α-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 levels, we have investigated pathways used in its release. We reveal that release inhibited removal of calcium augmented increasing or after treatment with Ca 2+ ionophore A23187. Furthermore, amino acid considerably reduced depletion thapsigargin-sensitive intracellular stores chelation 1,2-bis(2-aminophenoxy)ethane- N , ′, ′-tetraacetate–acetoxymethyl ester. Interestingly, also was markedly concanamycin A, vacuolar-type H + -ATPase inhibitor, indicating role for vesicular proton gradient transmitter storage/release. In addition, agonist-evoked tetanus neurotoxin. Finally, immunocytochemical sucrose density analysis revealed large fraction colocalized synaptobrevin/VAMP2, suggesting it stored VAMP2-bearing vesicles. summary, our study reveals cellular subserving highlights importance glial cell exocytotic pathway influencing CNS levels -serine.