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http://dx.doi.org/10.5352/JLS.2008.18.7.940

(γ-Aminobutyric Acid Transporter 2 Binds to the PDZ Domain of Mammalian Lin-7  

Seog, Dae-Hyun (Departments of Biochemistry, College of Medicine, Inje University)
Moon, II-Soo (Departments of Anatomy, College of Medicine, Dongguk University)
Publication Information
Journal of Life Science / v.18, no.7, 2008 , pp. 940-946 More about this Journal
Abstract
Neurotransmitter transporters, which remove neurotransmittesr from the synaptic cleft, are regulated by second messenger such as protein kinases and binding proteins. Neuronal ${\gamma}-aminobutyric$ acid transporters (GATs) are responsible for removing the inhibitory neurotransmitter ${\gamma}-aminobutyric$ acid (GABA) from the synaptic cleft. ${\gamma}-aminobutyric$ acid transporters 2 (GAT2/BGT1) is involved in regulating neurotransmitter recycling, but the mechanism how they are stabilized and regulated by the specific binding protein has not yet been elucidated. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the C-terminal region of GAT2 and found a specific interaction with the mammalian LIN-7b (MALS-2). MALS-2 protein bound to the tail region of GAT2 but not to other GAT members in the yeast two-hybrid assay. The "T-X-L" motif at the C-terminal end of GAT2 is essential for interaction with MALS-2. In addition, this protein showed specific interactions in the glutathione S-transferase (GST) pull-down assay. An antibody to GAT2 specifically co-immunoprecipitated MALS associated with GAT2 from mouse brain extracts. These results suggest that MALS may stabilize GAT2 in brain.
Keywords
${\gamma}-Aminobutyric$ acid${\gamma}-aminobutyric$ acid transporter; PDZ Domain; protein-protein interaction; mammalian LIN-7b;
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