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Gene Review

Slc6a11  -  solute carrier family 6 (neurotransmitter...

Mus musculus

Synonyms: D930045G19Rik, E130202I16Rik, GAT-3, GAT-4, GAT4, ...
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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


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].


  1. Zinc inhibition of gamma-aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory and inhibitory neurotransmission. Cohen-Kfir, E., Lee, W., Eskandari, S., Nelson, N. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Molecular characterization of four pharmacologically distinct gamma-aminobutyric acid transporters in mouse brain [corrected]. Liu, Q.R., López-Corcuera, B., Mandiyan, S., Nelson, H., Nelson, N. J. Biol. Chem. (1993) [Pubmed]
  3. Developmental expression of GABA transporters GAT1 and GAT4 suggests involvement in brain maturation. Jursky, F., Nelson, N. J. Neurochem. (1996) [Pubmed]
  4. Phylogenetic conservation of 4-aminobutyric acid (GABA) transporter isoforms. Cloning and pharmacological characterization of a GABA/beta-alanine transporter from Torpedo. Guimbal, C., Klostermann, A., Kilimann, M.W. Eur. J. Biochem. (1995) [Pubmed]
  5. Developmental expression of the neurotransmitter transporter GAT3. Jursky, F., Nelson, N. J. Neurosci. Res. (1999) [Pubmed]
  6. GABA-level increasing and anticonvulsant effects of three different GABA uptake inhibitors. Dalby, N.O. Neuropharmacology (2000) [Pubmed]
  7. Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05-2090, not acting preferentially on GAT-1. Dalby, N.O., Thomsen, C., Fink-Jensen, A., Lundbeck, J., Søkilde, B., Man, C.M., Sørensen, P.O., Meldrum, B. Epilepsy Res. (1997) [Pubmed]
  8. Novel properties of a mouse gamma-aminobutyric acid transporter (GAT4). Karakossian, M.H., Spencer, S.R., Gomez, A.Q., Padilla, O.R., Sacher, A., Loo, D.D., Nelson, N., Eskandari, S. J. Membr. Biol. (2005) [Pubmed]
  9. Physical and genetic maps of the deafwaddler region on distal mouse Chr 6. McKee-Johnson, J.W., Street, V.A., Erford, S.K., Robinson, L.C., Tempel, B.L. Genomics (1998) [Pubmed]
  10. Differential effect of pH on sodium binding by the various GABA transporters expressed in Xenopus oocytes. Grossman, T.R., Nelson, N. FEBS Lett. (2002) [Pubmed]
  11. GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone. Bolteus, A.J., Bordey, A. J. Neurosci. (2004) [Pubmed]
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