Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Bruno GasnierEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101902


Historical Background

Nerve terminals release neurotransmitters by exocytosis of synaptic vesicles, a process requiring prior accumulation within the vesicles. For “classical” (small-molecule) transmitters, this accumulation results from active transport of cytosolic transmitter across the vesicular membrane into the vesicle lumen. This transport involves a V-type proton-pumping ATPase, which acidifies and positively charges the vesicle lumen, and a secondary active transporter, which uses the proton electrochemical gradient across the vesicular membrane to accumulate specific transmitters (Edwards 2007).

The vesicular inhibitory amino acid transmitter (VIAAT), also known as vesicular GABA transporter (VGAT), ensures the vesicular uptake of the inhibitory amino acids GABA and glycine. VIAAT identification was initiated by genetic studies of GABAergic...

This is a preview of subscription content, log in to check access.


  1. Aubrey KR, Rossi FM, Ruivo R, Alboni S, Bellenchi GC, Le Goff A, Gasnier B, Supplisson S. The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype. J Neurosci. 2007;27:6273–81.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Chaudhry FA, Reimer RJ, Bellocchio EE, Danbolt NC, Osen KK, Edwards RH, Storm-Mathisen J. The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons. J Neurosci. 1998;18:9733–50.PubMedPubMedCentralCrossRefGoogle Scholar
  3. David A, Tiveron M-C, Defays A, Beclin C, Camosseto V, Gatti E, Cremer H, Pierre P. BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons. J Cell Sci. 2007;120:353–65.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Dumoulin A, Rostaing P, Bedet C, Lévi S, Isambert MF, Henry JP, Triller A, Gasnier B. Presence of the vesicular inhibitory amino acid transporter in GABAergic and glycinergic synaptic terminal boutons. J Cell Sci. 1999;112(Pt 6):811–23.PubMedPubMedCentralGoogle Scholar
  5. Edwards RH. The neurotransmitter cycle and quantal size. Neuron. 2007;55:835–58.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Egashira Y, Takase M, Watanabe S, Ishida J, Fukamizu A, Kaneko R, Yanagawa Y, Takamori S. Unique pH dynamics in GABAergic synaptic vesicles illuminates the mechanism and kinetics of GABA loading. Proc Natl Acad Sci USA. 2016;113:10702–7.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Farsi Z, Preobraschenski J, van den Bogaart G, Riedel D, Jahn R, Woehler A. Single-vesicle imaging reveals different transport mechanisms between glutamatergic and GABAergic vesicles. Science. 2016;351:981–4.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Jonas P. Corelease of two fast neurotransmitters at a central synapse. Science. 1998;281:419–24.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Juge N, Muroyama A, Hiasa M, Omote H, Moriyama Y. Vesicular inhibitory amino acid transporter is a Cl−/gamma-aminobutyrate co-transporter. J Biol Chem. 2009;284:35073–8.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Martens H, Weston MC, Boulland J-L, Gronborg M, Grosche J, Kacza J, Hoffmann A, Matteoli M, Takamori S, Harkany T, et al. Unique luminal localization of VGAT-C terminus allows for selective labeling of active cortical GABAergic synapses. J Neurosci. 2008;28:13125–31.PubMedPubMedCentralCrossRefGoogle Scholar
  11. McIntire SL, Jorgensen E, Kaplan J, Horvitz HR. The GABAergic nervous system of Caenorhabditis elegans. Nature. 1993a;364:337–41.PubMedPubMedCentralCrossRefGoogle Scholar
  12. McIntire SL, Jorgensen E, Horvitz HR. Genes required for GABA function in Caenorhabditis elegans. Nature. 1993b;364:334–7.PubMedPubMedCentralCrossRefGoogle Scholar
  13. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM. Identification and characterization of the vesicular GABA transporter. Nature. 1997;389:870–6.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Rees MI, Harvey K, Pearce BR, Chung S-K, Duguid IC, Thomas P, Beatty S, Graham GE, Armstrong L, Shiang R, et al. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat Genet. 2006;38:801–6.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Sagné C, El Mestikawy S, Isambert MF, Hamon M, Henry JP, Giros B, Gasnier B. Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases. FEBS Lett. 1997;417:177–83.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Saier J. Families of transmembrane transporters selective for amino acids and their derivatives. Microbiology. 2000;146:1775–95.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Santos MS, Park CK, Foss SM, Li H, Voglmaier SM. Sorting of the vesicular GABA transporter to functional vesicle pools by an atypical dileucine-like motif. J Neurosci. 2013;33:10634–46.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Schuske K, Palfreyman MT, Watanabe S, Jorgensen EM. UNC-46 is required for trafficking of the vesicular GABA transporter. Nat Neurosci. 2007;10:846–53.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Tian N, Petersen C, Kash S, Baekkeskov S, Copenhagen D, Nicoll R. The role of the synthetic enzyme GAD65 in the control of neuronal gamma-aminobutyric acid release. Proc Natl Acad Sci USA. 1999;96:12911–6.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Wojcik SM, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, Rhee JS. A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron. 2006;50:575–87.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Neurophotonics Laboratory (UMR 8250)Université Paris Descartes and Centre National de la Recherche ScientifiqueParisFrance