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 alpha and regulatory beta 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 alpha (Kir6.1/2) and beta (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 amino acid motif (RKR) can explain how assembly of an ion channel complex is coupled to intracellular trafficking.
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Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143-0725, USA.
Schwappach
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D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D008564:Membrane Potentials; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011955:Receptors, Drug / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D064233:Sulfonylurea Receptors; D014981:Xenopus
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; C577509:Abcc8 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate