Identification and characterization of the vesicular GABA transporter

McIntire, Steven L.; Reimer, Richard J.; Schuske, Kim; Edwards, Robert H.; Jørgensen, Erik M.

doi:10.1038/39908

Cited by 795 publications

(520 citation statements)

References 29 publications

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“…Accumulation of glycine in synaptic vesicles implies that a vesicular transporter must exist [66]. While no specific glycine transporter has so far been described, it seems that the vesicular transporter for GABA [67] is also localized to synaptic vesicles in glycinergic neurons [68]. Since this transporter also transport glycine ( fig.…”

Section: Presynaptic Release Machinery and Vesicular Glycine Uptakementioning

confidence: 99%

The glycinergic inhibitory synapse

Legendre¹

2001

CMLS, Cell. Mol. Life Sci.

475

474

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Glycine is one of the most important inhibitory neurotransmitters in the spinal cord and the brainstem, and glycinergic synapses have a well-established role in the regulation of locomotor behavior. Research over the last 15 years has yielded new insights on glycine neurotransmission. Glycinergic synapses are now known not to be restricted to the spinal cord and the brainstem. Presynaptic machinery for glycine release and uptake, the structure and function of postsynaptic receptors and the factors (both pre- and postsynaptic) which control the strength of glycinergic inhibition have been extensively studied. It is now established that glycinergic synapses can be excitatory in the immature brain and that some inhibitory synapses can corelease gamma-aminobutyric acid (GABA) and glycine. Moreover, the presence of glycine transporters on glial cells and the capacity of these cells to release glycine suggest that glycine may also act as a neuromodulator. Extensive molecular studies have revealed the presence of distinct subtypes of postsynaptic glycine receptors with different functional properties. Mechanisms of glycine receptors aggregation at postsynaptic sites during development are better understood and functional implications of variation in receptor number between postsynaptic sites are partly elucidated. Mutations of glycine receptor subunits have been shown to underly some human locomotor disorders, including the startle disease. Clearly, recent work on glycine receptor channels and the synapses at which they mediate inhibitory signalling in both young and adult animals necessitates an update of our vision of glycinergic inhibitory transmission.

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Section: Presynaptic Release Machinery and Vesicular Glycine Uptakementioning

confidence: 99%

The glycinergic inhibitory synapse

Legendre¹

2001

CMLS, Cell. Mol. Life Sci.

475

474

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“…This superfamily, initially discovered in plants [8,10] but also present in yeast [14] and animals [4,11,15], comprises diverse amino acid transporters coupled, or sensitive, to protons. In 2001 SagnØ et al identified the lysosomal amino acid transporter 1 (LYAAT1) in rat brain [16] and Boll et al identified PAT1 (orthologous to LYAAT1) and PAT2 cDNAs from mouse intestine and embryos, respectively in 2002 [3].…”

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confidence: 99%

“…Brief history of discovery SLC36 transporters were identified by homology-based cloning [3,16], using either the vesicular neurotransmitter transporter VIAAT/VGAT [11,15] or the yeast amino acid vacuolar transporter AVT3 [14] to search for novel mammalian members of the amino acid/auxin permease (AAAP) superfamily [21,23]. This superfamily, initially discovered in plants [8,10] but also present in yeast [14] and animals [4,11,15], comprises diverse amino acid transporters coupled, or sensitive, to protons.…”

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The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis

Boll

Daniel

Gasnier

2004

Pfl�gers Archiv European Journal of Physiology

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Whilst Na(+) has replaced H(+) as a major transport driving force at the plasma membrane of animal cells, the evolutionarily older H(+)-driven systems persist on endomembranes and at the plasma membrane of specialized cells. The first member of the SLC36 family, present in both intracellular and plasma membranes, was identified independently as a lysosomal amino acid transporter (LYAAT1) responsible for the export of lysosomal proteolysis products into the cytosol and as a proton/amino acid transporter (PAT1) responsible for the absorption of amino acids in the gut. In addition to LYAAT1/PAT1, the family comprises another characterized member, PAT2, and two orphan transporters. Both PAT1 and PAT2 mediate 1:1 symport of protons and small neutral amino acids such as glycine, alanine, and proline. Their mRNAs are broadly and differentially expressed in mammalian tissues. The PAT1 protein localizes to lysosomes in brain neurons, but is also found in the apical membrane of intestinal epithelial cells with a role in the absorption of amino acids from luminal protein digestion. In both cases, protons supplied by the lysosomal H(+)-ATPase or by the acidic microclimate of the brush border membrane drive transport of the amino acids into the cytosol. The subcellular localization and physiological role of PAT2 have still to be determined. SLC36 transporters are related distantly to other proton-coupled amino acid transporters, such as the vesicular neurotransmitter transporter VIAAT/VGAT (SLC32) and system N transporters (SLC38 family).

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“…Screening of genomic clones for their ability to rescue the unc-47 phenotype [15] and an independent search for transporter sequences in a region of the genome comprising unc-47 [19] led to the identification of UNC-47 and of a rodent orthologue. The mammalian protein was named the vesicular GABA transporter (VGAT [15]) or, to emphasize its role in both GABAergic and glycinergic neurons, the vesicular inhibitory amino acid transporter (VIAAT [19]). …”

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The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids

Gasnier

2004

Pfl�gers Archiv European Journal of Physiology

103

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The SLC32 family comprises a single member: the vesicular inhibitory amino acid transporter (VIAAT) or vesicular GABA transporter (VGAT). It belongs to a eukaryotic-specific superfamily of H(+)-coupled amino acid transporters, which also comprises the mammalian SLC36 and SLC38 transporters. VIAAT exchanges GABA or glycine for protons. It is present on synaptic vesicles of GABAergic and glycinergic neurons, and in some endocrine cells, where it ensures the H(+)-ATPase-driven uptake, and subsequent exocytotic release, of inhibitory amino acids. Despite a similar function in vesicular neurotransmitter loading, VIAAT is not related to the vesicular glutamate transporter (VGLUT, SLC17) or the vesicular monoamine transporter/vesicular acetylcholine transporter (VMAT/VACHT, SLC18) proteins.

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Identification and characterization of the vesicular GABA transporter

Cited by 795 publications

References 29 publications

The glycinergic inhibitory synapse

The glycinergic inhibitory synapse

The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis

The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids

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