Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify gliotransmission.
Journal of Neuroscience. 2013-02-20; 33(8): 3413-3423
DOI: 10.1523/JNEUROSCI.3497-12.2013
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1. J Neurosci. 2013 Feb 20;33(8):3413-23. doi: 10.1523/JNEUROSCI.3497-12.2013.
Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify
gliotransmission.
Martineau M(1), Shi T, Puyal J, Knolhoff AM, Dulong J, Gasnier B, Klingauf J,
Sweedler JV, Jahn R, Mothet JP.
Author information:
(1)Neurocentre Magendie, National Institute of Health and Medical Research, Unit
862 and University of Bordeaux, F-33077 Bordeaux, France.
Comment in
J Neurosci. 2013 Jun 19;33(25):10193-4.
Glial cells are increasingly recognized as active players that profoundly
influence neuronal synaptic transmission by specialized signaling pathways. In
particular, astrocytes have been shown recently to release small molecules, such
as the amino acids l-glutamate and d-serine as “gliotransmitters,” which directly
control the efficacy of adjacent synapses. However, it is still controversial
whether gliotransmitters are released from a cytosolic pool or by
Ca(2+)-dependent exocytosis from secretory vesicles, i.e., by a mechanism similar
to the release of synaptic vesicles in synapses. Here we report that rat cortical
astrocytes contain storage vesicles that display morphological and biochemical
features similar to neuronal synaptic vesicles. These vesicles share some, but
not all, membrane proteins with synaptic vesicles, including the SNARE (soluble
N-ethylmaleimide-sensitive factor attachment protein receptor) synaptobrevin 2,
and contain both l-glutamate and d-serine. Furthermore, they show uptake of
l-glutamate and d-serine that is driven by a proton electrochemical gradient.
d-Serine uptake is associated with vesicle acidification and is dependent on
chloride. Whereas l-serine is not transported, serine racemase, the synthesizing
enzyme for d-serine, is anchored to the membrane of the vesicles, allowing local
generation of d-serine. Finally, we reveal a previously unexpected mutual
vesicular synergy between d-serine and l-glutamate filling in glia vesicles. We
conclude that astrocytes contain vesicles capable of storing and releasing
d-serine, l-glutamate, and most likely other neuromodulators in an
activity-dependent manner.
DOI: 10.1523/JNEUROSCI.3497-12.2013
PMCID: PMC3772647
PMID: 23426669 [Indexed for MEDLINE]