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A Multimeric Membrane Protein Reveals 14‐3‐3 Isoform Specificity in Forward Transport in Yeast
Author(s) -
Michelsen Kai,
Mrowiec Thomas,
Duderstadt Karl E.,
Frey Steffen,
Minor Daniel L.,
Mayer Matthias P.,
Schwappach Blanche
Publication year - 2006
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2006.00430.x
Subject(s) - biology , gene isoform , protein targeting , endoplasmic reticulum , protein sorting signals , microbiology and biotechnology , saccharomyces cerevisiae , yeast , transport protein , signal peptide , membrane protein , biochemistry , peptide sequence , membrane , gene
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 (▵ bmh1 ▵ bmh2 ) and the individual ▵ bmh1 or ▵ bmh2 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.