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 journalArticle

41 Citations (Scopus)

Abstract

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 β-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)4353-4363
Number of pages11
JournalJOURNAL OF CELL SCIENCE
Volume119
Issue number20
DOIs
Publication statusPublished - 15 Oct 2006

Keywords

  • 14-3-3 proteins
  • ABC proteins
  • ER-localization signals
  • Inward rectifier potassium channels
  • Membrane protrein assembly
  • Quality control

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