Enhancement of TREK1 channel surface expression by protein-protein interaction with beta-COP.

TREK1 belongs to a family of two-pore-domain K(+) (K(2P)) channels and produce background currents that regulate cell excitability. In the present study, we identified a vesicle transport protein, beta-COP, as an interacting partner by yeast two-hybrid screening of a human brain cDNA library with N-terminal region of TREK1 (TREK1-N) as bait. Several in vitro and in vivo binding assays confirmed the protein-protein interaction between TREK1 and beta-COP. We also found that beta-COP was associated with TREK1 in native condition at the PC3 cells. When RFP-beta-COP was co-transfected with GFP-TREK1 into COS-7 cells, both proteins were found localized to the plasma membrane. In addition, the channel activity and surface expression of GFP-TREK1 increased dramatically by co-transfection with RFP-beta-COP. Surface expression of the TREK1 channel was also clearly reduced with the addition of beta-COP-specific shRNA. Collectively, these data suggest that beta-COP plays a critical role in the forward transport of TREK1 channel to the plasma membrane.