Golgin-97 Targets Ectopically Expressed Inward Rectifying Potassium Channel, Kir2.1, to the trans-Golgi Network in...

The inward rectifying potassium channel, Kir2.1, is selected as cargo at the trans-Golgi network (TGN) for export to the cell surface through a unique signal-dependent interaction with the AP1 clathrin-adaptor, but it is unknown how the channel is targeted at earlier stages in the secretory pathway for traffic to the TGN. Here we explore a mechanism. A systematic screen of Golgi tethers identified Golgin-97 as a Kir2.1 binding partner. In vitro protein-interaction studies revealed the interaction is direct, occurring between the GRIP domain of Golgin-97 and the cytoplasmic domain of Kir2.1. Imaging and interaction studies in COS-7 cells suggest that Golgi-97 binds to the channel en route through the Golgi. RNA interference-mediated knockdown of Golgin-97 prevented exit of Kir2.1 from the Golgi. These observations identify Golgin-97 as a Kir2.1 binding partner that is required for targeting the channel to the TGN. Based on our studies in COS-7 cells, we propose Golgi-97 facilitates formation of AP1-dependent export carriers for Kir2.1 by coupling anterograde delivery of Kir2.1 with retrograde recycling of AP-1 containing endosomes to the TGN.