High impact information on Slc6a12

• GAT-3, like GAT-1, localized to the apical membrane of MDCK cells while GAT-2, like BGT, localized to the basolateral membrane [1].
• The newly cloned GABA transporters were compared with two previously cloned GABA transporters, GAT1 and GAT2, in terms of molecular and pharmacological properties [2].
• The new GABA transporter, named GAT2, is highly homologous to the betaine transporter (BGT1) cloned from canine kidney [3].
• GAT2 transports betaine with a Km of about 200 microM, but no significant transport of beta-alanine could be detected [3].
• Expression of GAT2 in Xenopus oocytes revealed a Km of 79 microM for GABA uptake which is about 10-fold higher than that of the high affinity GABA transporter (GAT1) [3].

Biological context of Slc6a12

• 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 [1].
• SNAP-5114, a specific GABA transporter-2/3 (GAT-2/3) blocker, enhanced mIPSC frequencies, decreased PPR, and increased eIPSC amplitudes without changing eIPSC kinetics [4].
• The up-regulation of GAT2 protein was not affecting total GABA uptake but the hyperosmotic condition did change total GABA uptake possibly involving GAT1 [5].
• Taken together, these results indicate that astroglial GAT2 expression and function may be regulated by hyperosmolarity in cultured mouse astrocytes, suggesting a role of GAT2 in osmoregulation in neural cells [5].

Anatomical context of Slc6a12

• The transcripts of GAT2 were found in the cerebral cortex, cerebellum, and brainstem as well as in kidney [3].
• Mouse GAT2 mRNA was expressed only in proliferating and migrating cerebellar granule cells, whereas mGAT3 mRNA was absent from the brain and spinal cord throughout development [6].
• Moreover, confocal immunofluorescent microscopy of dual-labeled mouse brain sections demonstrated the colocalization of GAT2/BGT-1 and P-glycoprotein, a BBB-specific marker, on brain capillaries labeled with anti-GAT2/BGT-1 antibody and anti-P-glycoprotein antibody, respectively [7].
• GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier [7].
• When astrocytes were grown for 24 h under hyperosmotic conditions GAT2 protein was up-regulated 2-4-fold compared to the level of the isotonic control [5].

Associations of Slc6a12 with chemical compounds

• Specificity assays suggested that the transporter involved in delta-aminolevulinic acid incorporation is a BETA transporter, probably GAT-2 [8].
• Using Western Blotting the expression of the mouse GAT2 protein was investigated in astrocyte primary cultures exposed to a growth medium made hyperosmotic (353+/-2.5 mosmol/kg) by adding sodium chloride [5].

Other interactions of Slc6a12

• Low affinity GABA transporters GAT2 and GAT3 were inhibited most effectively by betaine and beta-alanine, respectively [2].
• In the presence of 20 microM GABA and at pH 7.5, the half-maximal uptake activity was 47, 120, 25 and 35 mM Na(+) for GAT1, GAT2, GAT3 and GAT4, respectively [9].

Analytical, diagnostic and therapeutic context of Slc6a12

• RT-PCR analysis showed that GAT2/BGT-1 mRNA was expressed in TM-BBB cells, whereas Western blot analysis showed that TM-BBB cells and mouse brain capillaries express GAT2/BGT-1 protein [7].

References