Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents

J Biol Chem. 2012 Oct 12;287(42):35733-46. doi: 10.1074/jbc.M112.368175. Epub 2012 Aug 15.

Abstract

The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [(3)H]taurine. Furthermore, most of the uptake of [(3)H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism*
  • Brain Chemistry
  • GABA Plasma Membrane Transport Proteins / genetics
  • GABA Plasma Membrane Transport Proteins / metabolism*
  • HEK293 Cells
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Humans
  • Kidney Cortex / cytology
  • Kidney Cortex / metabolism
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Rabbits
  • Rats
  • Rats, Wistar
  • Taurine / genetics
  • Taurine / metabolism*

Substances

  • GABA Plasma Membrane Transport Proteins
  • Slc6a12 protein, mouse
  • Slc6a13 protein, mouse
  • Slc6a13 protein, rat
  • Taurine