The GABA transporter GAT1 and the MAGUK protein Pals1: interaction, uptake modulation, and coexpression in the brain

GABAergic signaling in the CNS is terminated in part through uptake of GABA by GABA transporters. We used the yeast two-hybrid system to identify proteins that associate with the carboxy-terminus of the neuronal GABA transporter GAT1. We found an interaction between GAT1 and the MAGUK protein Pals1. When coexpressed in COS-7 cells, Palsl co-immunoprecipitates with GAT1. We demonstrate cellular coexpression of GAT1 and Palsl in the mouse hippocampas and striatum. Functionally, coexpression of GAT1 and Palsl in COS-7 cells increases [H-3]-GABA uptake by GAT1. The mechanism underlying increased uptake is increased levels of GAT1 protein. We hypothesize that Palsl contributes to the stability of the GAT1, thus promoting the expression level of the transporter protein. In the CNS, Palsl may stabilize GAT1 at appropriate levels in specific GABAergic neurons. (C) 2004 Elsevier Inc. All rights reserved.