Scavenging of 14-3-3 proteins reveals their involvement in the cell-surface transport of ATP-sensitive K+ channels

Katja Heusser, Hebao Yuan, Ioana Neagoe, Andrei I Tarasov, Frances M Ashcroft, Blanche Schwappach

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


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 languageEnglish
Pages (from-to)4353-63
Number of pages11
JournalJournal of Cell Science
Issue numberPt 20
Publication statusPublished - 15 Oct 2006


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


Dive into the research topics of 'Scavenging of 14-3-3 proteins reveals their involvement in the cell-surface transport of ATP-sensitive K+ channels'. Together they form a unique fingerprint.

Cite this