Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify gliotransmission

Magalie Martineau, Ting Shi, Julien Puyal, Ann M. Knolhoff, Jérôme Dulong, Bruno Gasnier, Jürgen Klingauf, Jonathan V. Sweedler, Reinhard Jahn, Jean Pierre Mothet

Research output: Contribution to journalArticlepeer-review


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 Ca2+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.

Original languageEnglish (US)
Pages (from-to)3413-3423
Number of pages11
JournalJournal of Neuroscience
Issue number8
StatePublished - Feb 20 2013

ASJC Scopus subject areas

  • Neuroscience(all)


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