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-fo rming alpha and regulatory beta subunits, but little is known about the mec hanisms that regulate the surface expression of different channel combinati ons. 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 alpha (Kir6.1/2) and beta (SUR1) subunits of the KATP complex. We sh ow that this novel motif for endoplasmic reticulum (ER) retention/retrieval is required at multiple stages of K-ATP assembly to restrict surface expre ssion to fully assembled and correctly regulated octameric channels. We con clude that exposure of a three amino acid motif (RKR) can explain how assem bly of an ion channel complex is coupled to intracellular trafficking.