A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels

Proper ion channel function often requires specific combinations of pore-forming α and regulatory β subunits, but little is known about the mechanisms that regulate the surface expression of different channel combinations. Our studies of ATP-sensitive K+ channel (K(ATP)) trafficking reveal an essential quality control function for a trafficking motif present in each of the α (Kir6.1/2) and β (SUR1) subunits of the K(ATP) complex. We show that this novel motif for endoplasmic reticulum (ER) retention/retrieval is required at multiple stages of K(ATP) assembly to restrict surface expression to fully assembled and correctly regulated octameric channels. We conclude that exposure of a three amine acid motif (RKR) can explain how assembly of an ion channel complex is coupled to intracellular trafficking.