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Arginine (Arg)-based endoplasmic reticulum (ER)-localization signals are involved in the quality control of different heteromultimeric membrane protein complexes. ATP-sensitive potassium (KATP) channels are unique because each subunit in the heterooctamer contains an Arg-based ER-localization signal. We have dissected the inactivation events that override the ER-localization activity of the eight peptide-sorting motifs. Employing a 14-3-3-scavenger construct to lower the availability of 14-3-3 proteins, we found that 14-3-3 proteins promote the cell-surface expression of heterologously expressed and native KATP channels. 14-3-3 proteins were detected in physical association with KATP channels in a pancreatic beta-cell line. Our results suggest that the Arg-based signal present in Kir6.2 is sterically masked by the SUR1 subunit. By contrast, 14-3-3 proteins functionally antagonized the Arg-based signal present in SUR1. The last ten amino acids were required for efficient 14-3-3 recruitment to multimeric forms of the Kir6.2 C-terminus. Channels containing a pore-forming subunit lacking these residues reached the cell surface inefficiently but were functionally indistinguishable from channels formed by the full-length subunits. In conclusion, 14-3-3 proteins promote the cell-surface transport of correctly assembled complexes but do not regulate the activity of KATP channels at the cell surface.

Original publication




Journal article


J Cell Sci

Publication Date





4353 - 4363


14-3-3 Proteins, Adenosine Triphosphate, Amino Acid Sequence, Animals, Arginine, Blotting, Western, COS Cells, Cell Line, Tumor, Cell Membrane, Chlorocebus aethiops, Dose-Response Relationship, Drug, Female, Gene Expression, Membrane Potentials, Membrane Proteins, Models, Biological, Molecular Sequence Data, Oocytes, Potassium Channels, Inwardly Rectifying, Protein Binding, Protein Transport, Rats, Recombinant Fusion Proteins, Signal Transduction, Xenopus