High impact information on Slc6a11

• 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].
• Immunolocalization of GAT4 in the hippocampus revealed dense localization in the CA1 and CA3 regions of the hippocampus, regions which are known to be heavily populated by zinc-containing glutamatergic neurons [1].
• High affinity GABA transporters GAT1 and GAT4 were more sensitive to inhibition by nipecotic acid [2].
• Similarly, GAT4 transports beta-alanine with Km of 99 microM and taurine with a Km of 1.4 mM [2].
• However, whereas GAT1 immunoreactivity was detected in distinct patterns in gray matter and growing axons, GAT4 immunoreactivity was found in a subset of radial glial cell fascicles [3].

Biological context of Slc6a11

• Two novel gamma-aminobutyric acid (GABA) transporters, GAT3 and GAT4, were cloned from the mouse neonatal brain cDNA library and expressed in Xenopus oocytes [2].
• 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 [4].

Anatomical context of Slc6a11

• GAT3 was localized to the meninges in developmental stages where two other GABA transporters, GAT1 and GAT4, were adjacently expressed [5].
• 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 [6].
• 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 [7].

Associations of Slc6a11 with chemical compounds

• Flufenamic acid inhibited GAT4 Na+/Cl-/GABA cotransport, ILi(leak), and ICl(leak), (Ki approximately 30 microM), and the voltage-induced presteady-state charge movements (Ki approximately 440 microM) [8].

Other interactions of Slc6a11

• A yeast artificial chromosome-based physical map suggests that the closest markers flanking the dfw locus, D6Mit11 (proximal) and Gat4, D6Mit55 (distal), are contained within 650-950 kb [9].
• The Km for GABA uptake by GAT3 was 18 microM and by GAT4 was 0.8 microM [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 [10].

Analytical, diagnostic and therapeutic context of Slc6a11

• Using immunohistochemistry, we found that astrocyte-like cells express the high-affinity GABA transporter subtype GAT4 on processes ensheathing neuronal precursors that contain GABA [11].

References