High impact information on Slc6a13

• We examined the effect of zinc on expressed GATs (GAT1, GAT2, GAT3, and GAT4) in Xenopus laevis oocytes by using tracer flux and electrophysiological methods [1].
• GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and it is not confined to the vicinity of GABAergic synapses in the cerebral cortex [2].
• These findings on the localization of GAT-3 in the cerebral cortex indicate that this transporter mediates GABA uptake into glial cells, and suggest that glial GABA uptake may function to limit the spread of GABA from the synapse, as well as to regulate overall GABA levels in the neuropil [2].
• Ultrastructural studies showed that GAT-3 ir was localized exclusively to astrocytic processes, which were found in the neuropil and adjacent to axon terminals having either symmetric or asymmetric specializations [2].
• We used electrophysiological and tracer uptake methods to examine the effect of valproate on a gamma-aminobutyric acid (GABA) transporter (mouse GAT3) expressed in Xenopus laevis oocytes [3].

Biological context of Slc6a13

• Two novel gamma-aminobutyric acid (GABA) transporters, GAT3 and GAT4, were cloned from the mouse neonatal brain cDNA library and expressed in Xenopus oocytes [4].
• The distribution of GAT-3 in these neurons after transfection was axonal as well as somatodendritic [5].
• In this report, we have localized the other two GABA transporters, GAT-2 and GAT-3, in transfected MDCK cells by GABA uptake, immunofluorescence, and cell surface biotinylation [5].
• According to similarity of amino acid sequence (77% identity), pharmacological properties, and tissue distribution (nervous-system-specific), it appears to be the counterpart of the beta-alanine-sensitive GABA transporter, GAT-B/GAT-3/GAT4, previously cloned from rat and mouse [6].

Anatomical context of Slc6a13

• The developmental distribution of GAT3 suggests involvement in central nervous system (CNS) maturation [7].
• The expression of GAT3 in the peripheral embryonic tissues was confined to the liver, to a layer of cells under the skin, to the mouse kidney, and to hipoccampal blood vessels only in late developmental stages [7].
• GAT3 was localized to the meninges in developmental stages where two other GABA transporters, GAT1 and GAT4, were adjacently expressed [7].
• We have investigated the cellular localization and distribution in the cerebral cortex of adult rats of one GABA transporter (GAT), GAT-3, by immunocytochemistry with affinity-purified polyclonal antibodies directed to its predicted C terminus that react monospecifically with a protein of approximately 70 kDa [2].
• The present study examines the effect of tiagabine (a selective inhibitor of GABA transporter 1, GAT-1), SNAP-5114 (a semi-selective inhibitor of rat GAT-3/mouse GAT4) and NNC 05-2045 (a non-selective GABA uptake inhibitor) in modulating GABA levels in the hippocampus and thalamus [8].

Associations of Slc6a13 with chemical compounds

• The Km for GABA uptake by GAT3 was 18 microM and by GAT4 was 0.8 microM [4].
• GAT3 also transports beta-alanine and taurine with Km of 28 and 540 microM, respectively [4].
• Uptake experiments indicated that valproate is not transported by mouse GAT3 in the absence or presence of GABA [3].
• In this report, we describe the developmental distribution of the y-aminobutyric acid transporter GAT3 which transports gamma-aminobutyric acid (GABA) and beta-alanine in a sodium chloride-dependent manner [7].
• Although a contribution of adrenergic agonistic effects cannot be entirely ruled out, it is proposed that inhibition of GAT-3 (mouse GAT4) is primarily responsible for the anticonvulsant action of these two nipecotic acid derivatives in MES, amygdala kindled rats and in sound-induced seizures in GEP-rats and DBA/2 mice [9].

Other interactions of Slc6a13

• Low affinity GABA transporters GAT2 and GAT3 were inhibited most effectively by betaine and beta-alanine, respectively [4].
• The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/- mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse [10].
• GAT-3 was localized within the astrocyte processes, sealing the GABAergic synapses in the Purkinje cell and granular layers after P10 [11].

References