A multimeric membrane protein reveals 14-3-3 isoform specificity in forward transport in yeast

Traffic. 2006 Jul;7(7):903-16. doi: 10.1111/j.1600-0854.2006.00430.x. Epub 2006 May 25.


Arginine (Arg)-based endoplasmic reticulum (ER) localization signals are sorting motifs involved in the quality control of multimeric membrane proteins. They are distinct from other ER localization signals like the C-terminal di-lysine [-K(X)KXX] signal. The Pmp2p isoproteolipid, a type I yeast membrane protein, reports faithfully on the activity of sorting signals when fused to a tail containing either an Arg-based motif or a -KKXX signal. This reporter reveals that the Arg-based ER localization signals from mammalian Kir6.2 and GB1 proteins are functional in yeast. Thus, the machinery involved in recognition of Arg-based signals is evolutionarily conserved. Multimeric presentation of the Arg-based signal from Kir6.2 on Pmp2p results in forward transport, which requires 14-3-3 proteins encoded in yeast by BMH1 and BMH2 in two isoforms. Comparison of a strain without any 14-3-3 proteins (Deltabmh2) and the individual Deltabmh1 or Deltabmh2 shows that the role of 14-3-3 in the trafficking of this multimeric Pmp2p reporter is isoform-specific. Efficient forward transport requires the presence of Bmh1p. The specific role of Bmh1p is not due to differences in abundance or affinity between the isoforms. Our results imply that 14-3-3 proteins mediate forward transport by a mechanism distinct from simple masking of the Arg-based signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Arginine / genetics
  • Arginine / metabolism
  • Endoplasmic Reticulum / metabolism
  • Gene Deletion
  • Gene Dosage
  • Genes, Reporter / genetics
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phenotype
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport
  • Proteolipids / chemistry
  • Proteolipids / genetics
  • Proteolipids / metabolism*
  • Receptors, GABA / genetics
  • Receptors, GABA / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction


  • 14-3-3 Proteins
  • Adaptor Proteins, Signal Transducing
  • BMH1 protein, S cerevisiae
  • BMH2 protein, S cerevisiae
  • Kir6.2 channel
  • Membrane Proteins
  • Nerve Tissue Proteins
  • PMP2 protein, S cerevisiae
  • Potassium Channels, Inwardly Rectifying
  • Protein Isoforms
  • Protein Subunits
  • Proteolipids
  • Receptors, GABA
  • Saccharomyces cerevisiae Proteins
  • Arginine