Document Detail


Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents.
MedLine Citation:
PMID:  22896705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yun Zhou; Silvia Holmseth; Caiying Guo; Bjørnar Hassel; Georg Höfner; Henrik S Huitfeldt; Klaus T Wanner; Niels C Danbolt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-15     Completed Date:  2012-12-31     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  35733-46     Citation Subset:  IM    
Affiliation:
Centre of Molecular Biology and Neuroscience, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / cytology,  metabolism*
Brain Chemistry
GABA Plasma Membrane Transport Proteins / genetics,  metabolism*
HEK293 Cells
Hepatocytes / cytology,  metabolism
Humans
Kidney Cortex / cytology,  metabolism
Kidney Tubules, Proximal / cytology,  metabolism
Liver / cytology,  metabolism*
Male
Mice
Mice, Knockout
Rabbits
Rats
Rats, Wistar
Taurine / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/GABA Plasma Membrane Transport Proteins; 0/Gat2 protein, rat; 0/Slc6a12 protein, mouse; 0/Slc6a13 protein, mouse; 107-35-7/Taurine
Comments/Corrections

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