@article {6936,
	title = {Proteome analysis and conditional deletion of the EAAT2 glutamate transporter provide evidence against a role of EAAT2 in pancreatic insulin secretion in mice.},
	journal = {The Journal of Biological Chemistry},
	volume = {289},
	year = {2014},
	month = {2014 Jan 17},
	pages = {1329-44},
	abstract = {<p>Islet function is incompletely understood in part because key steps in glutamate handling remain undetermined. The glutamate (excitatory amino acid) transporter 2 (EAAT2; Slc1a2) has been hypothesized to (a) provide islet cells with glutamate, (b) protect islet cells against high extracellular glutamate concentrations, (c) mediate glutamate release, or (d) control the pH inside insulin secretory granules. Here we floxed the EAAT2 gene to produce the first conditional EAAT2 knock-out mice. Crossing with Nestin-cyclization recombinase (Cre) eliminated EAAT2 from the brain, resulting in epilepsy and premature death, confirming the importance of EAAT2 for brain function and validating the genetic construction. Crossing with insulin-Cre lines (RIP-Cre and IPF1-Cre) to obtain pancreas-selective deletion did not appear to affect survival, growth, glucose tolerance, or β-cell number. We found (using TaqMan RT-PCR, immunoblotting, immunocytochemistry, and proteome analysis) that the EAAT2 levels were too low to support any of the four hypothesized functions. The proteome analysis detected more than 7,000 islet proteins of which more than 100 were transporters. Although mitochondrial glutamate transporters and transporters for neutral amino acids were present at high levels, all other transporters with known ability to transport glutamate were strikingly absent. Glutamate-metabolizing enzymes were abundant. The level of glutamine synthetase was 2 orders of magnitude higher than that of glutaminase. Taken together this suggests that the uptake of glutamate by islets from the extracellular fluid is insignificant and that glutamate is intracellularly produced. Glutamine synthetase may be more important for islets than assumed previously.</p>
},
	keywords = {Animals, Crosses, Excitatory Amino Acid Transporter 2, Gene Deletion, Genetic, Glutamic Acid, Insulin, Insulin-Secreting Cells, Knockout, Mice, Proteome},
	issn = {1083-351X},
	doi = {10.1074/jbc.M113.529065},
	author = {Zhou, Yun and Waanders, Leonie F and Holmseth, Silvia and Guo, Caiying and Berger, Urs V and Li, Yuchuan and Lehre, Anne-Catherine and Lehre, Knut P and Danbolt, Niels C}
}
@article {6922,
	title = {Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents.},
	journal = {The Journal of Biological Chemistry},
	volume = {287},
	year = {2012},
	month = {2012 Oct 12},
	pages = {35733-46},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Brain, Brain Chemistry, GABA Plasma Membrane Transport Proteins, HEK293 Cells, Hepatocytes, Humans, Kidney Cortex, Kidney Tubules, Knockout, Liver, Male, Mice, Proximal, Rabbits, Rats, Taurine, Wistar},
	issn = {1083-351X},
	doi = {10.1074/jbc.M112.368175},
	author = {Zhou, Yun and Holmseth, Silvia and Guo, Caiying and Hassel, Bj{\o}rnar and H{\"o}fner, Georg and Huitfeldt, Henrik S and Wanner, Klaus T and Danbolt, Niels C}
}
