The vesicular inhibitory amino acid transporter, VIAAT (also termed the vesicular GABA transporter VGAT), which is the sole representative of the SLC32 family, transports GABA, or glycine, into synaptic vesicles [2-3], and is a member of the structurally-defined amino acid-polyamine-organocation/APC clan composed of SLC32, SLC36 and SLC38 transporter families (see [8]). VIAAT was originally suggested to be composed of 10 TM segments with cytoplasmic N- and C-termini [6]. However, an alternative 9TM structure with the N terminus facing the cytoplasm and the C terminus residing in the synaptic vesicle lumen has subsequently been reported [5]. VIAAT acts as an antiporter for inhibitory amino acids and protons. The accumulation of GABA and glycine within vesicles is driven by both the chemical (ΔpH) and electrical (Δψ) components of the proton electrochemical gradient (Δµ_H+) established by a vacuolar H⁺-ATPase [6]. However, one study, [4], presented evidence that VIAAT is instead a Cl^-/GABA co-transporter. VIAAT co-exists with VGLUT1 (SLC17A7), or VGLUT2 (SLC17A6), in the synaptic vesicles of selected nerve terminals [1,10]. VIAAT knock out mice die between embryonic day 18.5 and birth [9]. In cultures of spinal cord neurones established from earlier embryos, the co-release of of GABA and glycine from synaptic vesicles is drastically reduced, providing direct evidence for the role of VIAAT in the sequestration of both transmitters [7,9].

* Key recommended reading is highlighted with an asterisk

* Anne C, Gasnier B. (2014) Vesicular neurotransmitter transporters: mechanistic aspects. Curr Top Membr, 73: 149-74. [PMID:24745982]

Erickson JD, De Gois S, Varoqui H, Schafer MK, Weihe E. (2006) Activity-dependent regulation of vesicular glutamate and GABA transporters: a means to scale quantal size. Neurochem Int, 48 (6-7): 643-9. [PMID:16546297]

Gasnier B. (2000) The loading of neurotransmitters into synaptic vesicles. Biochimie, 82 (4): 327-37. [PMID:10865121]

Gasnier B. (2004) The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids. Pflugers Arch, 447 (5): 756-9. [PMID:12750892]

* Schiöth HB, Roshanbin S, Hägglund MG, Fredriksson R. (2013) Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol Aspects Med, 34 (2-3): 571-85. [PMID:23506890]

1. Fattorini G, Verderio C, Melone M, Giovedì S, Benfenati F, Matteoli M, Conti F. (2009) VGLUT1 and VGAT are sorted to the same population of synaptic vesicles in subsets of cortical axon terminals. J Neurochem, 110 (5): 1538-46. [PMID:19627441]

2. Gasnier B. (2000) The loading of neurotransmitters into synaptic vesicles. Biochimie, 82 (4): 327-37. [PMID:10865121]

3. Gasnier B. (2004) The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids. Pflugers Arch, 447 (5): 756-9. [PMID:12750892]

4. Juge N, Muroyama A, Hiasa M, Omote H, Moriyama Y. (2009) Vesicular inhibitory amino acid transporter is a Cl-/gamma-aminobutyrate Co-transporter. J Biol Chem, 284 (50): 35073-8. [PMID:19843525]

5. Martens H, Weston MC, Boulland JL, Grønborg M, Grosche J, Kacza J, Hoffmann A, Matteoli M, Takamori S, Harkany T et al.. (2008) Unique luminal localization of VGAT-C terminus allows for selective labeling of active cortical GABAergic synapses. J Neurosci, 28 (49): 13125-31. [PMID:19052203]

6. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM. (1997) Identification and characterization of the vesicular GABA transporter. Nature, 389 (6653): 870-6. [PMID:9349821]

7. Saito K, Kakizaki T, Hayashi R, Nishimaru H, Furukawa T, Nakazato Y, Takamori S, Ebihara S, Uematsu M, Mishina M et al.. (2010) The physiological roles of vesicular GABA transporter during embryonic development: a study using knockout mice. Mol Brain, 3: 40. [PMID:21190592]

8. Schiöth HB, Roshanbin S, Hägglund MG, Fredriksson R. (2013) Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol Aspects Med, 34 (2-3): 571-85. [PMID:23506890]

9. Wojcik SM, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, Rhee JS. (2006) A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron, 50 (4): 575-87. [PMID:16701208]

10. Zander JF, Münster-Wandowski A, Brunk I, Pahner I, Gómez-Lira G, Heinemann U, Gutiérrez R, Laube G, Ahnert-Hilger G. (2010) Synaptic and vesicular coexistence of VGLUT and VGAT in selected excitatory and inhibitory synapses. J Neurosci, 30 (22): 7634-45. [PMID:20519538]