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

Neuron. 1999 Mar;22(3):537-48. doi: 10.1016/s0896-6273(00)80708-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adenosine Triphosphate / physiology*
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Membrane / metabolism
  • Cell Membrane / physiology
  • Electrophysiology
  • Endoplasmic Reticulum / physiology*
  • Flow Cytometry
  • Fluorescent Antibody Technique, Direct
  • Membrane Potentials
  • Mice
  • Molecular Sequence Data
  • Oocytes
  • Patch-Clamp Techniques
  • Potassium Channels / biosynthesis
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Rats
  • Receptors, Drug / biosynthesis
  • Receptors, Drug / metabolism
  • Signal Transduction / physiology*
  • Sulfonylurea Receptors
  • Xenopus

Substances

  • ATP-Binding Cassette Transporters
  • Abcc8 protein, mouse
  • Abcc8 protein, rat
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Adenosine Triphosphate